4-47320173-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000812.4(GABRB1):c.508T>C(p.Leu170=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.986 in 1,607,758 control chromosomes in the GnomAD database, including 781,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L170L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.97 (71759 hom., cov: 31)
  • Exomes 𝑓: 0.99 (709777 hom.)
• Consequence: GABRB1 NM_000812.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23

Genes affected

GABRB1 (HGNC:4081): (gamma-aminobutyric acid type A receptor subunit beta1) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 4-47320173-T-C is Benign according to our data. Variant chr4-47320173-T-C is described in ClinVar as [Benign]. Clinvar id is 1642812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB1	NM_000812.4	c.508T>C	p.Leu170=	synonymous_variant	5/9	ENST00000295454.8
GABRB1	XM_024453976.2	c.409T>C	p.Leu137=	synonymous_variant	5/9
GABRB1	XM_024453977.2	c.409T>C	p.Leu137=	synonymous_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB1	ENST00000295454.8	c.508T>C	p.Leu170=	synonymous_variant	5/9	1	NM_000812.4	P1
GABRB1	ENST00000510909.1	c.*176T>C		3_prime_UTR_variant, NMD_transcript_variant	4/5	4

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147638 AN: 152190 Hom.: 71710 Cov.: 31

Gnomad AFR AF: 0.919

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.976

GnomAD3 exomes AF: 0.986 AC: 247796 AN: 251420 Hom.: 122160 AF XY: 0.987 AC XY: 134069 AN XY: 135878

Gnomad AFR exome AF: 0.917

Gnomad AMR exome AF: 0.988

Gnomad ASJ exome AF: 0.976

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.996

Gnomad FIN exome AF: 0.998

Gnomad NFE exome AF: 0.988

Gnomad OTH exome AF: 0.985

GnomAD4 exome AF: 0.987 AC: 1437241 AN: 1455450 Hom.: 709777 Cov.: 35 AF XY: 0.988 AC XY: 715692 AN XY: 724532

Gnomad4 AFR exome AF: 0.916

Gnomad4 AMR exome AF: 0.988

Gnomad4 ASJ exome AF: 0.977

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.996

Gnomad4 FIN exome AF: 0.998

Gnomad4 NFE exome AF: 0.989

Gnomad4 OTH exome AF: 0.982

GnomAD4 genome AF: 0.970 AC: 147744 AN: 152308 Hom.: 71759 Cov.: 31 AF XY: 0.971 AC XY: 72303 AN XY: 74460

Gnomad4 AFR AF: 0.919

Gnomad4 AMR AF: 0.985

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 0.998

Gnomad4 NFE AF: 0.989

Gnomad4 OTH AF: 0.976

Alfa AF: 0.979 Hom.: 31795

Bravo AF: 0.966

Asia WGS AF: 0.994 AC: 3456 AN: 3478

EpiCase AF: 0.987

EpiControl AF: 0.986

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	13
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4482737; hg19: chr4-47322190;