rs971353

Variant names:

• chr4-47100877-C-T
• rs971353
• NM_000812.4:c.241-60372C>T

Variant summary

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

The NM_000812.4(GABRB1):​c.241-60372C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 151,734 control chromosomes in the GnomAD database, including 44,775 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 0.77 (44775 hom., cov: 30)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 7 publications found

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]

GABRB1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 45

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.241-60372C>T		intron_variant	Intron 3 of 8	ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2	c.142-60372C>T		intron_variant	Intron 3 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.142-60372C>T		intron_variant	Intron 4 of 9		XP_024309745.1
GABRB1	XM_017007986.3	c.241-60372C>T		intron_variant	Intron 3 of 4		XP_016863475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8	c.241-60372C>T		intron_variant	Intron 3 of 8	1	NM_000812.4	ENSP00000295454.3
GABRB1	ENST00000513567.5	c.142-60372C>T		intron_variant	Intron 3 of 3	4		ENSP00000426753.1
GABRB1	ENST00000510909.1	n.173-60372C>T		intron_variant	Intron 2 of 4	4		ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116198 AN: 151616 Hom.: 44732 Cov.: 30

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.766 AC: 116302 AN: 151734 Hom.: 44775 Cov.: 30 AF XY: 0.771 AC XY: 57140 AN XY: 74156

African (AFR) AF: 0.815 AC: 33739 AN: 41396

American (AMR) AF: 0.794 AC: 12082 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2870 AN: 3468

East Asian (EAS) AF: 0.493 AC: 2533 AN: 5136

South Asian (SAS) AF: 0.817 AC: 3934 AN: 4814

European-Finnish (FIN) AF: 0.798 AC: 8412 AN: 10536

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50167 AN: 67868

Other (OTH) AF: 0.775 AC: 1629 AN: 2102

Alfa AF: 0.756 Hom.: 29482

Bravo AF: 0.764

Asia WGS AF: 0.699 AC: 2435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.44
PhyloP100		0.34
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: rs971353; hg19: chr4-47102894;