7-1057638-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_001303473.2(GPR146):​c.123C>A​(p.Gly41Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 618,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G41G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: GPR146 NM_001303473.2 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=1.71 with no splicing effect.

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>A	p.Gly41Gly	synonymous	Exon 2 of 2	NP_001290402.1	Q96CH1
	CHLSN	NM_001318252.2	MANE Select	c.130-47495G>T		intron	N/A	NP_001305181.1	Q9BRJ6
	GPR146	NM_001303474.2		c.123C>A	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>A	p.Gly41Gly	synonymous	Exon 2 of 2	ENSP00000410743.2	Q96CH1
	GPR146	ENST00000397095.2	TSL:1	c.123C>A	p.Gly41Gly	synonymous	Exon 2 of 2	ENSP00000380283.1	Q96CH1
	CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.130-47495G>T		intron	N/A	ENSP00000380286.3	Q9BRJ6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000342 AC: 8 AN: 233688 AF XY: 0.0000628

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000243 AC: 15 AN: 618056 Hom.: 0 Cov.: 0 AF XY: 0.0000356 AC XY: 12 AN XY: 336956

African (AFR) AF: 0.00 AC: 0 AN: 17638

American (AMR) AF: 0.00 AC: 0 AN: 42828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20798

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

South Asian (SAS) AF: 0.000218 AC: 15 AN: 68804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3790

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 347664

Other (OTH) AF: 0.00 AC: 0 AN: 32716

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	4.5
DANN	Benign	0.61
PhyloP100		1.7
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

Other links and lift over

dbSNP: rs55698772; hg19: chr7-1097274;