5-170795881-A-G

Variant names:

• chr5-170795881-A-G
• rs1812910
• NM_014211.3:c.458+456A>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.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
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014211.3. 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
	GABRP	NM_014211.3	MANE Select	c.458+456A>G		intron	N/A	NP_055026.1	O00591
	GABRP	NM_001291985.2		c.458+456A>G		intron	N/A	NP_001278914.1	E7EWG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRP	ENST00000265294.9	TSL:1 MANE Select	c.458+456A>G		intron	N/A	ENSP00000265294.4	O00591
	GABRP	ENST00000518525.5	TSL:5	c.458+456A>G		intron	N/A	ENSP00000430100.1	O00591
	GABRP	ENST00000862231.1		c.458+456A>G		intron	N/A	ENSP00000532290.1

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

African (AFR) AF: 0.514 AC: 21325 AN: 41472

American (AMR) AF: 0.388 AC: 5925 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2168 AN: 5162

South Asian (SAS) AF: 0.378 AC: 1818 AN: 4804

European-Finnish (FIN) AF: 0.396 AC: 4190 AN: 10568

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26144 AN: 67948

Other (OTH) AF: 0.399 AC: 842 AN: 2112

Alfa AF: 0.389 Hom.: 15139

Bravo AF: 0.427

Asia WGS AF: 0.408 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.47
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: rs1812910; hg19: chr5-170222885;