chr7-47800789-C-T

Position:

• chr7-47800789-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138295.5(PKD1L1):​c.8053G>A​(p.Ala2685Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,840 control chromosomes in the GnomAD database, including 11,081 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1809 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9272 hom.)
• Consequence: PKD1L1 NM_138295.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.48

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-AS1 (HGNC:21911): (PKD1L1 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0051170588).
• BP6: Variant 7-47800789-C-T is Benign according to our data. Variant chr7-47800789-C-T is described in ClinVar as [Benign]. Clinvar id is 1262863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD1L1	NM_138295.5	c.8053G>A	p.Ala2685Thr	missense_variant	54/57	ENST00000289672.7
PKD1L1-AS1	NR_161269.1	n.153+5346C>T		intron_variant, non_coding_transcript_variant
PKD1L1	XM_017011798.3	c.8230G>A	p.Ala2744Thr	missense_variant	55/59
PKD1L1-AS1	NR_161268.1	n.153+5346C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD1L1	ENST00000289672.7	c.8053G>A	p.Ala2685Thr	missense_variant	54/57	1	NM_138295.5	P2
PKD1L1-AS1	ENST00000623971.3	n.153+5346C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21144 AN: 151926 Hom.: 1807 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.0861

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0859

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.129

GnomAD3 exomes AF: 0.0996 AC: 25051 AN: 251478 Hom.: 1525 AF XY: 0.0981 AC XY: 13339 AN XY: 135916

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.0648

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.0350

Gnomad SAS exome AF: 0.0581

Gnomad FIN exome AF: 0.0839

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.108 AC: 157849 AN: 1461796 Hom.: 9272 Cov.: 33 AF XY: 0.107 AC XY: 77600 AN XY: 727198

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.0688

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.0392

Gnomad4 SAS exome AF: 0.0585

Gnomad4 FIN exome AF: 0.0835

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.139 AC: 21172 AN: 152044 Hom.: 1809 Cov.: 32 AF XY: 0.136 AC XY: 10113 AN XY: 74342

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.0331

Gnomad4 SAS AF: 0.0579

Gnomad4 FIN AF: 0.0859

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.127

Alfa AF: 0.119 Hom.: 2091

Bravo AF: 0.144

TwinsUK AF: 0.102 AC: 378

ALSPAC AF: 0.127 AC: 491

ESP6500AA AF: 0.233 AC: 1025

ESP6500EA AF: 0.114 AC: 977

ExAC AF: 0.104 AC: 12600

Asia WGS AF: 0.0700 AC: 247 AN: 3478

EpiCase AF: 0.119

EpiControl AF: 0.112

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Heterotaxy, visceral, 8, autosomal Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.031
DANN	Benign	0.58
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.020
Sift	Benign	0.64	T
Sift4G	Benign	0.12	T
Polyphen		0.14	B
Vest4		0.034
MPC		0.094
ClinPred		0.0069	T
GERP RS		-9.6
Varity_R		0.022
gMVP		0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs13231277; hg19: chr7-47840387; COSMIC: COSV51842574;