rs373684171

Variant names:

• chr16-2093745-AG-A
• rs373684171
• NM_001009944.3:c.10822-8delC

Your query was ambiguous. Multiple possible variants found:

• chr16-2093745-AG-A
• chr16-2093745-AG-AGG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001009944.3(PKD1):​c.10822-8delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,576,710 control chromosomes in the GnomAD database, including 5 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (5 hom.)
• Consequence: PKD1 NM_001009944.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.39
• 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 -16 ACMG points.

• BP6: Variant 16-2093745-AG-A is Benign according to our data. Variant chr16-2093745-AG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 256897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000453 (69/152200) while in subpopulation EAS AF = 0.0118 (61/5182). AF 95% confidence interval is 0.00941. There are 0 homozygotes in GnomAd4. There are 43 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 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.10822-8delC		splice_region intron	N/A	NP_001009944.3
	PKD1	NM_000296.4		c.10819-8delC		splice_region intron	N/A	NP_000287.4
	PKD1-AS1	NR_135175.1		n.303+738delG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	ENST00000262304.9	TSL:1 MANE Select	c.10822-8delC		splice_region intron	N/A	ENSP00000262304.4
	PKD1	ENST00000423118.5	TSL:1	c.10819-8delC		splice_region intron	N/A	ENSP00000399501.1
	PKD1	ENST00000472659.1	TSL:3	n.259-8delC		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152082 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00113 AC: 212 AN: 188094 AF XY: 0.000958

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0139

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000808

GnomAD4 exome AF: 0.000265 AC: 378 AN: 1424510 Hom.: 5 Cov.: 32 AF XY: 0.000272 AC XY: 192 AN XY: 705840

African (AFR) AF: 0.00 AC: 0 AN: 32532

American (AMR) AF: 0.0000487 AC: 2 AN: 41098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25554

East Asian (EAS) AF: 0.00761 AC: 287 AN: 37700

South Asian (SAS) AF: 0.000510 AC: 42 AN: 82406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1092918

Other (OTH) AF: 0.000747 AC: 44 AN: 58908

GnomAD4 genome AF: 0.000453 AC: 69 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.000578 AC XY: 43 AN XY: 74426

African (AFR) AF: 0.00 AC: 0 AN: 41530

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000423

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Polycystic kidney disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs373684171; hg19: chr16-2143746; COSMIC: COSV99239436; COSMIC: COSV99239436;