chr7-1057638-C-T

Variant names:

• chr7-1057638-C-T
• rs55698772
• NM_001303473.2:c.123C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001303473.2(GPR146):​c.123C>T​(p.Gly41Gly) 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
• Publications: 2 publications found

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]

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

ENSG00000257607 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303473.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR146	NM_001303473.2	MANE Select	c.123C>T	p.Gly41Gly	synonymous	Exon 2 of 2	NP_001290402.1	Q96CH1
	CHLSN	NM_001318252.2	MANE Select	c.130-47495G>A		intron	N/A	NP_001305181.1	Q9BRJ6
	GPR146	NM_001303474.2		c.123C>T	p.Gly41Gly	synonymous	Exon 3 of 3	NP_001290403.1	Q96CH1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR146	ENST00000444847.2	TSL:2 MANE Select	c.123C>T	p.Gly41Gly	synonymous	Exon 2 of 2	ENSP00000410743.2	Q96CH1
	GPR146	ENST00000397095.2	TSL:1	c.123C>T	p.Gly41Gly	synonymous	Exon 2 of 2	ENSP00000380283.1	Q96CH1
	CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.130-47495G>A		intron	N/A	ENSP00000380286.3	Q9BRJ6

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

GnomAD2 exomes AF: 0.00647 AC: 1513 AN: 233688 AF XY: 0.00683

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 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

African (AFR) AF: 0.00136 AC: 24 AN: 17638

American (AMR) AF: 0.00427 AC: 183 AN: 42828

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 378 AN: 20798

East Asian (EAS) AF: 0.00 AC: 0 AN: 35788

South Asian (SAS) AF: 0.00549 AC: 378 AN: 68804

European-Finnish (FIN) AF: 0.00760 AC: 365 AN: 48030

Middle Eastern (MID) AF: 0.0148 AC: 56 AN: 3788

European-Non Finnish (NFE) AF: 0.00822 AC: 2859 AN: 347658

Other (OTH) AF: 0.00795 AC: 260 AN: 32716

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

African (AFR) AF: 0.00118 AC: 49 AN: 41574

American (AMR) AF: 0.00451 AC: 69 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4826

European-Finnish (FIN) AF: 0.00885 AC: 94 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00735 AC: 500 AN: 68028

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00719 Hom.: 3

Bravo AF: 0.00492

Asia WGS AF: 0.00491 AC: 18 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.3
DANN	Benign	0.54
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=98/2	polymorphism

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: rs55698772; hg19: chr7-1097274;