rs10517179

Variant names:

• chr4-47107059-C-T
• rs10517179
• NM_000812.4:c.241-54190C>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.241-54190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 152,090 control chromosomes in the GnomAD database, including 783 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 0.063 (783 hom., cov: 32)
• Consequence: GABRB1 NM_000812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	NM_000812.4	c.241-54190C>T		intron_variant	Intron 3 of 8	ENST00000295454.8	NP_000803.2
GABRB1	XM_024453976.2	c.142-54190C>T		intron_variant	Intron 3 of 8		XP_024309744.1
GABRB1	XM_024453977.2	c.142-54190C>T		intron_variant	Intron 4 of 9		XP_024309745.1
GABRB1	XM_017007986.3	c.241-54190C>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.241-54190C>T		intron_variant	Intron 3 of 8	1	NM_000812.4	ENSP00000295454.3
GABRB1	ENST00000513567.5	c.142-54190C>T		intron_variant	Intron 3 of 3	4		ENSP00000426753.1
GABRB1	ENST00000510909.1	n.173-54190C>T		intron_variant	Intron 2 of 4	4		ENSP00000426766.1

Frequencies

GnomAD3 genomes AF: 0.0632 AC: 9599 AN: 151972 Hom.: 782 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00709

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0631 AC: 9603 AN: 152090 Hom.: 783 Cov.: 32 AF XY: 0.0644 AC XY: 4789 AN XY: 74352

African (AFR) AF: 0.185 AC: 7670 AN: 41478

American (AMR) AF: 0.0193 AC: 295 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3472

East Asian (EAS) AF: 0.0242 AC: 125 AN: 5168

South Asian (SAS) AF: 0.0583 AC: 281 AN: 4824

European-Finnish (FIN) AF: 0.0519 AC: 551 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00711 AC: 483 AN: 67962

Other (OTH) AF: 0.0497 AC: 105 AN: 2112

Alfa AF: 0.0185 Hom.: 211

Bravo AF: 0.0635

Asia WGS AF: 0.0620 AC: 216 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	0.52
DANN	Benign	0.64
PhyloP100		-2.0
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: rs10517179; hg19: chr4-47109076;