rs7192711

Variant names:

• chr16-2093752-G-A
• rs7192711
• NM_001009944.3:c.10822-14C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001009944.3(PKD1):​c.10822-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00621 in 1,570,898 control chromosomes in the GnomAD database, including 483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (275 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (208 hom.)
• Consequence: PKD1 NM_001009944.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.405
• Publications: 3 publications found

Genes affected

PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]

PKD1-AS1 (HGNC:56035): (PKD1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-2093752-G-A is Benign according to our data. Variant chr16-2093752-G-A is described in ClinVar as Benign. ClinVar VariationId is 256896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3	c.10822-14C>T		intron_variant	Intron 36 of 45	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9	c.10822-14C>T		intron_variant	Intron 36 of 45	1	NM_001009944.3	ENSP00000262304.4

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4864 AN: 152146 Hom.: 274 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.00815 AC: 1467 AN: 179918 AF XY: 0.00640

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.00644

Gnomad ASJ exome AF: 0.00572

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000677

Gnomad OTH exome AF: 0.00623

GnomAD4 exome AF: 0.00343 AC: 4865 AN: 1418634 Hom.: 208 Cov.: 32 AF XY: 0.00300 AC XY: 2107 AN XY: 702524

African (AFR) AF: 0.109 AC: 3539 AN: 32340

American (AMR) AF: 0.00676 AC: 272 AN: 40252

Ashkenazi Jewish (ASJ) AF: 0.00717 AC: 183 AN: 25508

East Asian (EAS) AF: 0.00 AC: 0 AN: 37332

South Asian (SAS) AF: 0.000195 AC: 16 AN: 81938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46526

Middle Eastern (MID) AF: 0.00489 AC: 28 AN: 5726

European-Non Finnish (NFE) AF: 0.000333 AC: 363 AN: 1090314

Other (OTH) AF: 0.00790 AC: 464 AN: 58698

GnomAD4 genome AF: 0.0321 AC: 4885 AN: 152264 Hom.: 275 Cov.: 33 AF XY: 0.0316 AC XY: 2356 AN XY: 74460

African (AFR) AF: 0.110 AC: 4586 AN: 41520

American (AMR) AF: 0.0122 AC: 186 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68006

Other (OTH) AF: 0.0227 AC: 48 AN: 2112

Alfa AF: 0.0127 Hom.: 86

Bravo AF: 0.0363

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 25, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic kidney disease, adult type Benign:1

Jan 28, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic kidney disease Benign:1

-

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

The PKD1 c.10822-14C>T variant was identified in 3 of 460 proband chromosomes (frequency: 0.007) from American individuals or families with ADPKD (Rossetti 2012). The variant was also identified in dbSNP (ID: rs7192711) as “With Benign allele”, the ADPKD Mutation Database (classification likely neutral), the 1000 Genomes Project in 165 of 5015 chromosomes (frequency: 0.03), HAPMAP-YRI in 26 of 226 chromosomes (frequency: 0.115), HAPMAP-ASW in 12 of 98 chromosomes (frequency: 0.122), HAPMAP-LWK in 22 of 189 chromosomes (frequency: 0.122), the NHLBI GO Exome Sequencing Project in 8 of 8552 European American alleles (frequency: 0.0009) and in 453 of 4362 African American alleles (frequency: 0.1), and in the Exome Aggregation Consortium database (August 8, 2016) in 531 of 33314 chromosomes (29 homozgyous) (frequency: 0.02) in the following populations: African in 466 (29 homozygotes) of 3264 chromosomes (frequency: 0.1), Latino in 31 of 2608 chromosomes (frequency: 0.01), Other in 2 of 280 chromosomes (frequency: 0.007), European (Non-Finnish) in 110 of 64720 chromosomes (frequency: 0.002), and South Asian in 1 of 9322 chromosomes (frequency: 0.0001), but was not seen in East Asian and Finnish and populations. The variant was also identified in Clinvitae (classification benign), ClinVar (classification benign, submitter Prevention Genetics), but was not in GeneInsight-COGR, PKD1-LOVD, and PKD1-LOVD 3.0. The variant was identified by our laboratory in 1 individual with ADPKD, co-occurring with a pathogenic PKD1 variant (c.12178C>T, p.Gln4060X), increasing the likelihood that the variant does not have clinical significance. The c.10822-14C>T variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. In addition, five of five in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a greater than 10% difference in splicing. In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.3
DANN	Benign	0.54
PhyloP100		0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7192711; hg19: chr16-2143753;