NM_001009944.3:c.11156+13G>A

Variant names:

• chr16-2092941-C-T
• rs142616270
• NM_001009944.3:c.11156+13G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001009944.3(PKD1):​c.11156+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,612,910 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (8 hom., cov: 33)
  • Exomes 𝑓: 0.012 (145 hom.)
• Consequence: PKD1 NM_001009944.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.140
• Publications: 2 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=-0.87).
• BP6: Variant 16-2092941-C-T is Benign according to our data. Variant chr16-2092941-C-T is described in ClinVar as Benign. ClinVar VariationId is 256898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0102 (1553/152324) while in subpopulation NFE AF = 0.0137 (933/68034). AF 95% confidence interval is 0.013. There are 8 homozygotes in GnomAd4. There are 775 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	NM_001009944.3	MANE Select	c.11156+13G>A		intron	N/A	NP_001009944.3
	PKD1	NM_000296.4		c.11153+13G>A		intron	N/A	NP_000287.4
	PKD1-AS1	NR_135175.1		n.232C>T		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	ENST00000262304.9	TSL:1 MANE Select	c.11156+13G>A		intron	N/A	ENSP00000262304.4
	PKD1	ENST00000423118.5	TSL:1	c.11153+13G>A		intron	N/A	ENSP00000399501.1
	PKD1	ENST00000472659.1	TSL:3	n.606G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1552 AN: 152206 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00824

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.00910

GnomAD2 exomes AF: 0.0107 AC: 2672 AN: 250636 AF XY: 0.0103

Gnomad AFR exome AF: 0.00265

Gnomad AMR exome AF: 0.00839

Gnomad ASJ exome AF: 0.0175

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0289

Gnomad NFE exome AF: 0.0128

Gnomad OTH exome AF: 0.0124

GnomAD4 exome AF: 0.0124 AC: 18047 AN: 1460586 Hom.: 145 Cov.: 32 AF XY: 0.0121 AC XY: 8756 AN XY: 726580

African (AFR) AF: 0.00272 AC: 91 AN: 33480

American (AMR) AF: 0.00863 AC: 386 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 436 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000765 AC: 66 AN: 86256

European-Finnish (FIN) AF: 0.0265 AC: 1382 AN: 52236

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.0135 AC: 14960 AN: 1111916

Other (OTH) AF: 0.0117 AC: 704 AN: 60374

GnomAD4 genome AF: 0.0102 AC: 1553 AN: 152324 Hom.: 8 Cov.: 33 AF XY: 0.0104 AC XY: 775 AN XY: 74474

African (AFR) AF: 0.00298 AC: 124 AN: 41570

American (AMR) AF: 0.00823 AC: 126 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.0289 AC: 307 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0137 AC: 933 AN: 68034

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.0147 Hom.: 6

Bravo AF: 0.00855

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Autosomal dominant polycystic kidney disease (1)
-	-	1	not provided (1)
-	-	1	Polycystic kidney disease, adult type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.59
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism

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: rs142616270; hg19: chr16-2142942;