7-47800712-C-G

Position:

• chr7-47800712-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138295.5(PKD1L1):​c.8130G>C​(p.Gln2710His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,614,188 control chromosomes in the GnomAD database, including 693 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 (★).

• Frequency:
  • Genomes: 𝑓 0.019 (47 hom., cov: 32)
  • Exomes 𝑓: 0.023 (646 hom.)
• Consequence: PKD1L1 NM_138295.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.307

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022588074).
• BP6: Variant 7-47800712-C-G is Benign according to our data. Variant chr7-47800712-C-G is described in ClinVar as [Benign]. Clinvar id is 2027216.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD1L1	NM_138295.5	c.8130G>C	p.Gln2710His	missense_variant	54/57	ENST00000289672.7
PKD1L1-AS1	NR_161269.1	n.153+5269C>G		intron_variant, non_coding_transcript_variant
PKD1L1	XM_017011798.3	c.8307G>C	p.Gln2769His	missense_variant	55/59
PKD1L1-AS1	NR_161268.1	n.153+5269C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD1L1	ENST00000289672.7	c.8130G>C	p.Gln2710His	missense_variant	54/57	1	NM_138295.5	P2
PKD1L1-AS1	ENST00000623971.3	n.153+5269C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2898 AN: 152194 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.00405

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.00734

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.0299 AC: 7511 AN: 251470 Hom.: 194 AF XY: 0.0318 AC XY: 4326 AN XY: 135910

Gnomad AFR exome AF: 0.00338

Gnomad AMR exome AF: 0.0568

Gnomad ASJ exome AF: 0.0606

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.0703

Gnomad FIN exome AF: 0.00744

Gnomad NFE exome AF: 0.0210

Gnomad OTH exome AF: 0.0274

GnomAD4 exome AF: 0.0229 AC: 33471 AN: 1461876 Hom.: 646 Cov.: 32 AF XY: 0.0245 AC XY: 17840 AN XY: 727242

Gnomad4 AFR exome AF: 0.00272

Gnomad4 AMR exome AF: 0.0583

Gnomad4 ASJ exome AF: 0.0568

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0729

Gnomad4 FIN exome AF: 0.00719

Gnomad4 NFE exome AF: 0.0189

Gnomad4 OTH exome AF: 0.0241

GnomAD4 genome AF: 0.0191 AC: 2908 AN: 152312 Hom.: 47 Cov.: 32 AF XY: 0.0202 AC XY: 1504 AN XY: 74474

Gnomad4 AFR AF: 0.00404

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0729

Gnomad4 FIN AF: 0.00734

Gnomad4 NFE AF: 0.0202

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0229 Hom.: 37

Bravo AF: 0.0203

TwinsUK AF: 0.0170 AC: 63

ALSPAC AF: 0.0156 AC: 60

ESP6500AA AF: 0.00431 AC: 19

ESP6500EA AF: 0.0209 AC: 180

ExAC AF: 0.0291 AC: 3536

Asia WGS AF: 0.0290 AC: 99 AN: 3478

EpiCase AF: 0.0228

EpiControl AF: 0.0222

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 20, 2024

- -

PKD1L1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.11
DANN	Benign	0.34
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.066
Sift	Benign	0.56	T
Sift4G	Benign	0.62	T
Polyphen		0.0020	B
Vest4		0.045
MutPred		0.52		Loss of ubiquitination at K2707 (P = 0.1099);
MPC		0.088
ClinPred		0.00071	T
GERP RS		0.51
Varity_R		0.028
gMVP		0.14

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: rs146576726; hg19: chr7-47840310;