rs7660336

Variant names:

• chr4-46927651-G-C
• rs7660336
• NM_000809.4:c.*574C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-46927651-G-C
• chr4-46927651-G-T

Variant summary

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

The NM_000809.4(GABRA4):​c.*574C>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 0.521 in 152,320 control chromosomes in the GnomAD database, including 20,804 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 0.52 (20751 hom., cov: 32)
  • Exomes 𝑓: 0.51 (53 hom.)
• Consequence: GABRA4 NM_000809.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 10 publications found

Genes affected

GABRA4 (HGNC:4078): (gamma-aminobutyric acid type A receptor subunit alpha4) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. This gene encodes subunit alpha-4, which is involved in the etiology of autism and eventually increases autism risk through interaction with another subunit, gamma-aminobutyric acid receptor beta-1 (GABRB1). Alternatively spliced transcript variants encoding different isoforms have been found in this gene.[provided by RefSeq, Feb 2011]

GABRA4 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Illumina

ENSG00000299086 (HGNC:58780):

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 (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000809.4. 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
	GABRA4	NM_000809.4	MANE Select	c.*574C>G		3_prime_UTR	Exon 9 of 9	NP_000800.2
	GABRA4	NM_001204266.2		c.*574C>G		3_prime_UTR	Exon 9 of 9	NP_001191195.1
	GABRA4	NM_001204267.2		c.*574C>G		3_prime_UTR	Exon 8 of 8	NP_001191196.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA4	ENST00000264318.4	TSL:1 MANE Select	c.*574C>G		3_prime_UTR	Exon 9 of 9	ENSP00000264318.3	P48169
	GABRA4	ENST00000900310.1		c.*574C>G		3_prime_UTR	Exon 8 of 8	ENSP00000570369.1
	ENSG00000299086	ENST00000760386.1		n.173-793G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78970 AN: 151758 Hom.: 20717 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.514 AC: 228 AN: 444 Hom.: 53 Cov.: 0 AF XY: 0.507 AC XY: 139 AN XY: 274

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.750 AC: 3 AN: 4

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.535 AC: 199 AN: 372

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.355 AC: 22 AN: 62

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.521 AC: 79061 AN: 151876 Hom.: 20751 Cov.: 32 AF XY: 0.521 AC XY: 38668 AN XY: 74230

African (AFR) AF: 0.474 AC: 19631 AN: 41438

American (AMR) AF: 0.566 AC: 8614 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3468

East Asian (EAS) AF: 0.662 AC: 3417 AN: 5162

South Asian (SAS) AF: 0.548 AC: 2640 AN: 4814

European-Finnish (FIN) AF: 0.549 AC: 5790 AN: 10540

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35735 AN: 67912

Other (OTH) AF: 0.505 AC: 1065 AN: 2108

Alfa AF: 0.402 Hom.: 1087

Bravo AF: 0.519

Asia WGS AF: 0.591 AC: 2051 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.62
PhyloP100		-0.031
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: rs7660336; hg19: chr4-46929668;