rs1497568

Variant names:

• chr4-46038741-A-G
• rs1497568
• NM_173536.4:c.*2247T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-46038741-A-G
• chr4-46038741-A-T

Variant summary

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

The NM_173536.4(GABRG1):​c.*2247T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 150,978 control chromosomes in the GnomAD database, including 20,093 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 0.51 (20093 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GABRG1 NM_173536.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• Publications: 7 publications found

Genes affected

GABRG1 (HGNC:4086): (gamma-aminobutyric acid type A receptor subunit gamma1) The protein encoded by this gene belongs to the ligand-gated ionic channel family. It is an integral membrane protein and plays an important role in inhibiting neurotransmission by binding to the benzodiazepine receptor and opening an integral chloride channel. This gene is clustered with three other family members on chromosome 4. [provided by RefSeq, Jul 2008]

GABRG1 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: G2P

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 = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.*2247T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2	c.*2247T>C		3_prime_UTR_variant	Exon 7 of 7		XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.*2247T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.508 AC: 76614 AN: 150860 Hom.: 20056 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.474

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: 0.508 AC: 76721 AN: 150978 Hom.: 20093 Cov.: 32 AF XY: 0.507 AC XY: 37356 AN XY: 73694

African (AFR) AF: 0.636 AC: 26263 AN: 41268

American (AMR) AF: 0.474 AC: 7185 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1453 AN: 3454

East Asian (EAS) AF: 0.358 AC: 1839 AN: 5144

South Asian (SAS) AF: 0.329 AC: 1584 AN: 4816

European-Finnish (FIN) AF: 0.552 AC: 5786 AN: 10476

Middle Eastern (MID) AF: 0.333 AC: 96 AN: 288

European-Non Finnish (NFE) AF: 0.460 AC: 31020 AN: 67382

Other (OTH) AF: 0.472 AC: 990 AN: 2096

Alfa AF: 0.460 Hom.: 18296

Bravo AF: 0.511

Asia WGS AF: 0.391 AC: 1349 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.71
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: rs1497568; hg19: chr4-46040758;