7-1058177-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001303473.2(GPR146):c.662A>G(p.Asp221Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00485 in 740,280 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (28 hom.)
• Consequence: GPR146 NM_001303473.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.80

Genes affected

GPR146 (HGNC:21718): (G protein-coupled receptor 146) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01095292).
• BP6: Variant 7-1058177-A-G is Benign according to our data. Variant chr7-1058177-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2657178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR146	NM_001303473.2	c.662A>G	p.Asp221Gly	missense_variant	2/2	ENST00000444847.2
C7orf50	NM_001318252.2	c.130-48034T>C		intron_variant		ENST00000397098.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR146	ENST00000444847.2	c.662A>G	p.Asp221Gly	missense_variant	2/2	2	NM_001303473.2	P1
C7orf50	ENST00000397098.8	c.130-48034T>C		intron_variant		1	NM_001318252.2	P1
	ENST00000549241.1	n.1085T>C		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 571 AN: 152150 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00697

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00328 AC: 633 AN: 192828 Hom.: 2 AF XY: 0.00336 AC XY: 352 AN XY: 104854

Gnomad AFR exome AF: 0.000482

Gnomad AMR exome AF: 0.000640

Gnomad ASJ exome AF: 0.00430

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00575

Gnomad NFE exome AF: 0.00583

Gnomad OTH exome AF: 0.00270

GnomAD4 exome AF: 0.00513 AC: 3017 AN: 588010 Hom.: 28 Cov.: 0 AF XY: 0.00527 AC XY: 1686 AN XY: 320146

Gnomad4 AFR exome AF: 0.000517

Gnomad4 AMR exome AF: 0.000682

Gnomad4 ASJ exome AF: 0.00342

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00616

Gnomad4 NFE exome AF: 0.00764

Gnomad4 OTH exome AF: 0.00359

GnomAD4 genome AF: 0.00374 AC: 570 AN: 152270 Hom.: 3 Cov.: 33 AF XY: 0.00350 AC XY: 261 AN XY: 74480

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000916

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.00696

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00746 Hom.: 2

Bravo AF: 0.00271

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.000229 AC: 1

ESP6500EA AF: 0.00432 AC: 37

ExAC AF: 0.00290 AC: 347

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

C7orf50: BS2; GPR146: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	20
Dann	Uncertain	0.98
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.053
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.14
Sift	Benign	0.12	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.50	.;P
Vest4		0.20
MVP		0.59
MPC		0.14
ClinPred		0.061	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.20
gMVP		0.52

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: rs140289241; hg19: chr7-1097813;