7-47791672-A-T

Variant names:

• chr7-47791672-A-T
• rs6463447
• NM_138295.5:c.8526+955T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138295.5(PKD1L1):​c.8526+955T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,016 control chromosomes in the GnomAD database, including 37,578 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (37578 hom., cov: 32)
• Consequence: PKD1L1 NM_138295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 1 publications found

Genes affected

PKD1L1 (HGNC:18053): (polycystin 1 like 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family containing 11 transmembrane domains, a receptor for egg jelly (REJ) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. The encoded protein may play a role in the male reproductive system. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

PKD1L1 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 8, autosomal

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L1	NM_138295.5	c.8526+955T>A		intron_variant	Intron 56 of 56	ENST00000289672.7	NP_612152.1
PKD1L1	XM_017011798.3	c.8703+955T>A		intron_variant	Intron 57 of 58		XP_016867287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L1	ENST00000289672.7	c.8526+955T>A		intron_variant	Intron 56 of 56	1	NM_138295.5	ENSP00000289672.2

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106479 AN: 151898 Hom.: 37557 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.707

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.701 AC: 106542 AN: 152016 Hom.: 37578 Cov.: 32 AF XY: 0.701 AC XY: 52116 AN XY: 74300

African (AFR) AF: 0.652 AC: 26990 AN: 41424

American (AMR) AF: 0.686 AC: 10487 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2606 AN: 3472

East Asian (EAS) AF: 0.641 AC: 3313 AN: 5172

South Asian (SAS) AF: 0.618 AC: 2974 AN: 4812

European-Finnish (FIN) AF: 0.750 AC: 7927 AN: 10570

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49864 AN: 67974

Other (OTH) AF: 0.708 AC: 1494 AN: 2110

Alfa AF: 0.720 Hom.: 4947

Bravo AF: 0.693

Asia WGS AF: 0.626 AC: 2177 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.50
PhyloP100		-1.7
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: rs6463447; hg19: chr7-47831270;