rs1862242

Variant names:

• chr5-170806258-A-G
• rs1862242
• NM_014211.3:c.679+405A>G

Variant summary

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

The NM_014211.3(GABRP):​c.679+405A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,142 control chromosomes in the GnomAD database, including 6,729 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 0.26 (6729 hom., cov: 32)
• Consequence: GABRP NM_014211.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 4 publications found

Genes affected

GABRP (HGNC:4089): (gamma-aminobutyric acid type A receptor subunit pi) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. The subunit encoded by this gene is expressed in several non-neuronal tissues including the uterus and ovaries. This subunit can assemble with known GABA A receptor subunits, and the presence of this subunit alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRP	NM_014211.3	c.679+405A>G		intron_variant	Intron 7 of 9	ENST00000265294.9	NP_055026.1
GABRP	NM_001291985.2	c.679+405A>G		intron_variant	Intron 7 of 8		NP_001278914.1
GABRP	XM_024446012.2	c.679+405A>G		intron_variant	Intron 7 of 9		XP_024301780.1
GABRP	XM_005265872.2	c.442+405A>G		intron_variant	Intron 5 of 7		XP_005265929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRP	ENST00000265294.9	c.679+405A>G		intron_variant	Intron 7 of 9	1	NM_014211.3	ENSP00000265294.4
GABRP	ENST00000518525.5	c.679+405A>G		intron_variant	Intron 8 of 10	5		ENSP00000430100.1
GABRP	ENST00000519598.1	c.679+405A>G		intron_variant	Intron 7 of 9	5		ENSP00000430772.1
GABRP	ENST00000519385.5	c.679+405A>G		intron_variant	Intron 7 of 8	2		ENSP00000430727.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40132 AN: 152024 Hom.: 6706 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.264 AC: 40204 AN: 152142 Hom.: 6729 Cov.: 32 AF XY: 0.263 AC XY: 19559 AN XY: 74394

African (AFR) AF: 0.472 AC: 19588 AN: 41470

American (AMR) AF: 0.257 AC: 3933 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3468

East Asian (EAS) AF: 0.151 AC: 781 AN: 5174

South Asian (SAS) AF: 0.342 AC: 1652 AN: 4826

European-Finnish (FIN) AF: 0.131 AC: 1387 AN: 10594

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11466 AN: 68006

Other (OTH) AF: 0.259 AC: 547 AN: 2110

Alfa AF: 0.203 Hom.: 14427

Bravo AF: 0.279

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.82
PhyloP100		-0.30
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: rs1862242; hg19: chr5-170233262;