chr4-46100556-A-G

Variant names:

• chr4-46100556-A-G
• rs10517150
• NM_173536.4:c.105-3207T>C

Variant summary

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

The NM_173536.4(GABRG1):​c.105-3207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 151,414 control chromosomes in the GnomAD database, including 941 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 0.080 (941 hom., cov: 29)
• Consequence: GABRG1 NM_173536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 4 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4	c.105-3207T>C		intron_variant	Intron 1 of 8	ENST00000295452.5	NP_775807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5	c.105-3207T>C		intron_variant	Intron 1 of 8	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12163 AN: 151302 Hom.: 938 Cov.: 29

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.0148

Gnomad EAS AF: 0.000586

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0805 AC: 12186 AN: 151414 Hom.: 941 Cov.: 29 AF XY: 0.0819 AC XY: 6052 AN XY: 73940

African (AFR) AF: 0.196 AC: 8112 AN: 41348

American (AMR) AF: 0.0825 AC: 1250 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.0148 AC: 51 AN: 3456

East Asian (EAS) AF: 0.000587 AC: 3 AN: 5110

South Asian (SAS) AF: 0.0282 AC: 136 AN: 4816

European-Finnish (FIN) AF: 0.0844 AC: 889 AN: 10528

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0238 AC: 1611 AN: 67698

Other (OTH) AF: 0.0611 AC: 128 AN: 2096

Alfa AF: 0.0643 Hom.: 101

Bravo AF: 0.0832

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.0
DANN	Benign	0.75
PhyloP100		1.2
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: rs10517150; hg19: chr4-46102573;