7-1057638-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001303473.2(GPR146):c.123C>T(p.Gly41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 770,380 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0073 (28 hom.)
• Consequence: GPR146 NM_001303473.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.71

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 7-1057638-C-T is Benign according to our data. Variant chr7-1057638-C-T is described in ClinVar as [Benign]. Clinvar id is 770731.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.71 with no splicing effect.
• 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.123C>T	p.Gly41=	synonymous_variant	2/2	ENST00000444847.2
C7orf50	NM_001318252.2	c.130-47495G>A		intron_variant		ENST00000397098.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR146	ENST00000444847.2	c.123C>T	p.Gly41=	synonymous_variant	2/2	2	NM_001303473.2	P1
C7orf50	ENST00000397098.8	c.130-47495G>A		intron_variant		1	NM_001318252.2	P1
	ENST00000549241.1	n.1497+127G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00541 AC: 823 AN: 152214 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00885

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00735

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00647 AC: 1513 AN: 233688 Hom.: 6 AF XY: 0.00683 AC XY: 870 AN XY: 127376

Gnomad AFR exome AF: 0.00114

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.0169

Gnomad EAS exome AF: 0.0000570

Gnomad SAS exome AF: 0.00600

Gnomad FIN exome AF: 0.00696

Gnomad NFE exome AF: 0.00792

Gnomad OTH exome AF: 0.00901

GnomAD4 exome AF: 0.00729 AC: 4503 AN: 618048 Hom.: 28 Cov.: 0 AF XY: 0.00724 AC XY: 2439 AN XY: 336952

Gnomad4 AFR exome AF: 0.00136

Gnomad4 AMR exome AF: 0.00427

Gnomad4 ASJ exome AF: 0.0182

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00549

Gnomad4 FIN exome AF: 0.00760

Gnomad4 NFE exome AF: 0.00822

Gnomad4 OTH exome AF: 0.00795

GnomAD4 genome AF: 0.00541 AC: 824 AN: 152332 Hom.: 3 Cov.: 33 AF XY: 0.00561 AC XY: 418 AN XY: 74490

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.00885

Gnomad4 NFE AF: 0.00735

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00719 Hom.: 3

Bravo AF: 0.00492

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	5.3
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs55698772; hg19: chr7-1097274;