7-41690102-C-G

Variant names:

• chr7-41690102-C-G
• rs1390964419
• NM_002192.4:c.829G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002192.4(INHBA):​c.829G>C​(p.Gly277Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. G277S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INHBA NM_002192.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

Genes affected

INHBA (HGNC:6066): (inhibin subunit beta A) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate a subunit of the dimeric activin and inhibin protein complexes. These complexes activate and inhibit, respectively, follicle stimulating hormone secretion from the pituitary gland. The encoded protein also plays a role in eye, tooth and testis development. Elevated expression of this gene may be associated with cancer cachexia in human patients. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16402116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INHBA	NM_002192.4	c.829G>C	p.Gly277Arg	missense_variant	Exon 3 of 3	ENST00000242208.5	NP_002183.1
INHBA	XM_017012174.2	c.829G>C	p.Gly277Arg	missense_variant	Exon 3 of 3		XP_016867663.2
INHBA	XM_047420335.1	c.829G>C	p.Gly277Arg	missense_variant	Exon 4 of 4		XP_047276291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INHBA	ENST00000242208.5	c.829G>C	p.Gly277Arg	missense_variant	Exon 3 of 3	1	NM_002192.4	ENSP00000242208.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.56	.;.;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.1	L;L;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.14	N;N;.
REVEL	Benign	0.26
Sift	Benign	0.036	D;D;.
Sift4G	Uncertain	0.0050	D;D;.
Polyphen		0.58	P;P;P
Vest4		0.12
MutPred		0.34		Gain of methylation at G277 (P = 0.0098);Gain of methylation at G277 (P = 0.0098);Gain of methylation at G277 (P = 0.0098);
MVP		0.62
MPC		0.94
ClinPred		0.30	T
GERP RS		5.6
Varity_R		0.057
gMVP		0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs1390964419; hg19: chr7-41729700;