rs10060148

Variant names:

• chr5-161332137-G-A
• rs10060148
• NM_001371727.1:c.833-1010C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-161332137-G-A
• chr5-161332137-G-T

Variant summary

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

The NM_001371727.1(GABRB2):​c.833-1010C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 132,894 control chromosomes in the GnomAD database, including 437 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 0.078 (437 hom., cov: 23)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 2 publications found

Genes affected

GABRB2 (HGNC:4082): (gamma-aminobutyric acid type A receptor subunit beta2) 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 2 subunit. It is mapped to chromosome 5q34 in a cluster comprised of genes encoding alpha 1 and gamma 2 subunits of the GABA A receptor. Alternative splicing of this gene generates 2 transcript variants, differing by a 114 bp insertion. [provided by RefSeq, Jul 2008]

GABRB2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 92

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.833-1010C>T		intron_variant	Intron 7 of 9	ENST00000393959.6	NP_001358656.1
GABRB2	NM_021911.3	c.833-1010C>T		intron_variant	Intron 8 of 10		NP_068711.1
GABRB2	NM_000813.3	c.833-1010C>T		intron_variant	Intron 8 of 9		NP_000804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.833-1010C>T		intron_variant	Intron 7 of 9	1	NM_001371727.1	ENSP00000377531.1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 10323 AN: 132852 Hom.: 437 Cov.: 23

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.0369

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0688

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

GnomAD4 genome AF: 0.0777 AC: 10321 AN: 132894 Hom.: 437 Cov.: 23 AF XY: 0.0807 AC XY: 5081 AN XY: 62946

African (AFR) AF: 0.0950 AC: 3224 AN: 33942

American (AMR) AF: 0.0646 AC: 766 AN: 11850

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 283 AN: 3400

East Asian (EAS) AF: 0.0366 AC: 168 AN: 4596

South Asian (SAS) AF: 0.0152 AC: 65 AN: 4272

European-Finnish (FIN) AF: 0.193 AC: 1324 AN: 6852

Middle Eastern (MID) AF: 0.0990 AC: 20 AN: 202

European-Non Finnish (NFE) AF: 0.0653 AC: 4253 AN: 65154

Other (OTH) AF: 0.0676 AC: 118 AN: 1746

Alfa AF: 0.0277 Hom.: 24

Bravo AF: 0.0689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.71
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: rs10060148; hg19: chr5-160759144;