4-47031698-C-T

Variant names:

• chr4-47031698-C-T
• rs1021581518
• NM_000812.4:c.47C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000812.4(GABRB1):​c.47C>T​(p.Pro16Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P16H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GABRB1 NM_000812.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90
• Publications: 0 publications found

Genes affected

GABRB1 (HGNC:4081): (gamma-aminobutyric acid type A receptor subunit beta1) 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 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]

GABRB1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 45

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000301858 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18759781).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000812.4. 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
	GABRB1	NM_000812.4	MANE Select	c.47C>T	p.Pro16Leu	missense	Exon 1 of 9	NP_000803.2	X5DNL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.47C>T	p.Pro16Leu	missense	Exon 1 of 9	ENSP00000295454.3	P18505-1
	GABRB1	ENST00000509366.5	TSL:1	n.148C>T		non_coding_transcript_exon	Exon 1 of 4
	GABRB1	ENST00000513567.5	TSL:4	c.-19-216C>T		intron	N/A	ENSP00000426753.1	D6REM0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.42
Sift	Benign	0.092	T
Sift4G	Benign	0.72	T
Polyphen		0.0090	B
Vest4		0.24
MutPred		0.45		Loss of helix (P = 0.1706)
MVP		0.93
MPC		0.016
ClinPred		0.75	D
GERP RS		4.5
PromoterAI		0.025	Neutral
Varity_R		0.13
gMVP		0.62
Mutation Taster		=274/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1021581518; hg19: chr4-47033715;