chr5-170806258-A-G

Position:

• chr5-170806258-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GABRP	NM_014211.3	c.679+405A>G		intron_variant		ENST00000265294.9	NP_055026.1
GABRP	NM_001291985.2	c.679+405A>G		intron_variant			NP_001278914.1
GABRP	XM_005265872.2	c.442+405A>G		intron_variant			XP_005265929.1
GABRP	XM_024446012.2	c.679+405A>G		intron_variant			XP_024301780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRP	ENST00000265294.9	c.679+405A>G		intron_variant		1	NM_014211.3	ENSP00000265294	P1
GABRP	ENST00000518525.5	c.679+405A>G		intron_variant		5		ENSP00000430100	P1
GABRP	ENST00000519385.5	c.679+405A>G		intron_variant		2		ENSP00000430727
GABRP	ENST00000519598.1	c.679+405A>G		intron_variant		5		ENSP00000430772

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

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.259

Alfa AF: 0.191 Hom.: 5426

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

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: rs1862242; hg19: chr5-170233262;