NM_153002.3:c.234-917C>A

Variant names:

• chr3-120194341-G-T
• rs4676822
• NM_153002.3:c.234-917C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153002.3(GPR156):​c.234-917C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,292 control chromosomes in the GnomAD database, including 62,621 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.91 (62621 hom., cov: 32)
• Consequence: GPR156 NM_153002.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 2 publications found

Genes affected

GPR156 (HGNC:20844): (G protein-coupled receptor 156) G protein-coupled receptors (GPCRs) are a large superfamily of cell surface receptors characterized by 7 helical transmembrane domains, together with N-terminal extracellular and C-terminal intracellular domains.[supplied by OMIM, Mar 2008]

GPR156 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 121

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR156	NM_153002.3	c.234-917C>A		intron_variant	Intron 3 of 9	ENST00000464295.6	NP_694547.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR156	ENST00000464295.6	c.234-917C>A		intron_variant	Intron 3 of 9	5	NM_153002.3	ENSP00000417261.1
GPR156	ENST00000461057.1	c.234-917C>A		intron_variant	Intron 2 of 8	1		ENSP00000418758.1
GPR156	ENST00000495912.5	n.234-20871C>A		intron_variant	Intron 2 of 3	5		ENSP00000417191.1

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137926 AN: 152174 Hom.: 62567 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.913

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.906 AC: 138042 AN: 152292 Hom.: 62621 Cov.: 32 AF XY: 0.905 AC XY: 67423 AN XY: 74466

African (AFR) AF: 0.880 AC: 36544 AN: 41548

American (AMR) AF: 0.925 AC: 14165 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 3234 AN: 3470

East Asian (EAS) AF: 0.921 AC: 4766 AN: 5176

South Asian (SAS) AF: 0.854 AC: 4125 AN: 4828

European-Finnish (FIN) AF: 0.937 AC: 9949 AN: 10618

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62251 AN: 68024

Other (OTH) AF: 0.913 AC: 1926 AN: 2110

Alfa AF: 0.899 Hom.: 7973

Bravo AF: 0.908

Asia WGS AF: 0.896 AC: 3115 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.75
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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: rs4676822; hg19: chr3-119913188;