chr5-170795881-A-G

Position:

• chr5-170795881-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.458+456A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,008 control chromosomes in the GnomAD database, including 13,813 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 0.42 (13813 hom., cov: 31)
• Consequence: GABRP NM_014211.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRP	NM_014211.3	c.458+456A>G		intron_variant		ENST00000265294.9	NP_055026.1
GABRP	NM_001291985.2	c.458+456A>G		intron_variant			NP_001278914.1
GABRP	XM_005265872.2	c.221+456A>G		intron_variant			XP_005265929.1
GABRP	XM_024446012.2	c.458+456A>G		intron_variant			XP_024301780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRP	ENST00000265294.9	c.458+456A>G		intron_variant		1	NM_014211.3	ENSP00000265294	P1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63929 AN: 151890 Hom.: 13787 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.421 AC: 63992 AN: 152008 Hom.: 13813 Cov.: 31 AF XY: 0.420 AC XY: 31199 AN XY: 74286

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.399

Alfa AF: 0.388 Hom.: 12952

Bravo AF: 0.427

Asia WGS AF: 0.408 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.59

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: rs1812910; hg19: chr5-170222885;