NM_001371727.1:c.*1104T>G

Variant names:

• chr5-161292977-A-C
• rs592403
• NM_001371727.1:c.*1104T>G

Variant summary

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

The NM_001371727.1(GABRB2):​c.*1104T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,008 control chromosomes in the GnomAD database, including 18,505 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 0.46 (18505 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GABRB2 NM_001371727.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371727.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	NM_001371727.1	MANE Select	c.*1104T>G		3_prime_UTR	Exon 10 of 10	NP_001358656.1
	GABRB2	NM_021911.3		c.*1104T>G		3_prime_UTR	Exon 11 of 11	NP_068711.1
	GABRB2	NM_000813.3		c.*1104T>G		3_prime_UTR	Exon 10 of 10	NP_000804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	ENST00000393959.6	TSL:1 MANE Select	c.*1104T>G		3_prime_UTR	Exon 10 of 10	ENSP00000377531.1
	GABRB2	ENST00000675081.1		n.*1988T>G		non_coding_transcript_exon	Exon 8 of 8	ENSP00000502207.1
	GABRB2	ENST00000274547.7	TSL:5	c.*1104T>G		3_prime_UTR	Exon 11 of 11	ENSP00000274547.2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70146 AN: 151892 Hom.: 18473 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.465

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.462 AC: 70227 AN: 152008 Hom.: 18505 Cov.: 32 AF XY: 0.460 AC XY: 34163 AN XY: 74308

African (AFR) AF: 0.721 AC: 29896 AN: 41454

American (AMR) AF: 0.524 AC: 8000 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1140 AN: 3468

East Asian (EAS) AF: 0.428 AC: 2213 AN: 5166

South Asian (SAS) AF: 0.382 AC: 1843 AN: 4820

European-Finnish (FIN) AF: 0.294 AC: 3104 AN: 10560

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22642 AN: 67956

Other (OTH) AF: 0.463 AC: 977 AN: 2110

Alfa AF: 0.385 Hom.: 38519

Bravo AF: 0.495

Asia WGS AF: 0.444 AC: 1543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.65
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs592403; hg19: chr5-160719984;