rs424740

Variant names:

• chr5-162154029-T-A
• rs424740
• NM_198904.4:c.*661T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-162154029-T-A
• chr5-162154029-T-C
• chr5-162154029-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198903.2(GABRG2):​c.*661T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,596 control chromosomes in the GnomAD database, including 16,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16062 hom., cov: 32)
  • Exomes 𝑓: 0.34 (40 hom.)
• Consequence: GABRG2 NM_198903.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91
• Publications: 13 publications found

Genes affected

GABRG2 (HGNC:4087): (gamma-aminobutyric acid type A receptor subunit gamma2) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GABRG2 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 74

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• febrile seizures, familial, 8

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Dravet syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• generalized epilepsy with febrile seizures plus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• self-limited epilepsy with centrotemporal spikes

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-162154029-T-A is Benign according to our data. Variant chr5-162154029-T-A is described in ClinVar as Benign. ClinVar VariationId is 352656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198903.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG2	NM_198904.4	MANE Select	c.*661T>A		3_prime_UTR	Exon 10 of 10	NP_944494.1
	GABRG2	NM_198903.2		c.*661T>A		3_prime_UTR	Exon 11 of 11	NP_944493.2
	GABRG2	NM_001375343.1		c.*661T>A		3_prime_UTR	Exon 10 of 10	NP_001362272.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG2	ENST00000639213.2	TSL:1 MANE Select	c.*661T>A		3_prime_UTR	Exon 10 of 10	ENSP00000491909.2
	GABRG2	ENST00000414552.6	TSL:1	c.*661T>A		3_prime_UTR	Exon 11 of 11	ENSP00000410732.2
	GABRG2	ENST00000639111.2	TSL:1	c.*661T>A		3_prime_UTR	Exon 9 of 9	ENSP00000492125.2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68308 AN: 151870 Hom.: 16032 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.340 AC: 207 AN: 608 Hom.: 40 Cov.: 0 AF XY: 0.320 AC XY: 116 AN XY: 362

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.364 AC: 8 AN: 22

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.125 AC: 1 AN: 8

European-Finnish (FIN) AF: 0.321 AC: 117 AN: 364

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 78 AN: 208

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.450 AC: 68391 AN: 151988 Hom.: 16062 Cov.: 32 AF XY: 0.451 AC XY: 33486 AN XY: 74270

African (AFR) AF: 0.570 AC: 23632 AN: 41486

American (AMR) AF: 0.345 AC: 5250 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1502 AN: 3468

East Asian (EAS) AF: 0.676 AC: 3488 AN: 5158

South Asian (SAS) AF: 0.514 AC: 2474 AN: 4816

European-Finnish (FIN) AF: 0.367 AC: 3873 AN: 10554

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26704 AN: 67952

Other (OTH) AF: 0.408 AC: 863 AN: 2114

Alfa AF: 0.431 Hom.: 1929

Bravo AF: 0.448

Asia WGS AF: 0.559 AC: 1937 AN: 3464

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	EPILEPSY, CHILDHOOD ABSENCE, SUSCEPTIBILITY TO, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.75
PhyloP100		1.9
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: rs424740; hg19: chr5-161581035;