rs376838491

Variant names:

• chr7-41700281-C-G
• rs376838491
• NM_002192.4:c.94G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-41700281-C-G
• chr7-41700281-C-T

Variant summary

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

The NM_002192.4(INHBA):​c.94G>C​(p.Ala32Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A32T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: INHBA NM_002192.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54
• Publications: 0 publications found

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]

INHBA-AS1 (HGNC:40303): (INHBA antisense RNA 1)

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=0.15559867).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002192.4. 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
	INHBA	NM_002192.4	MANE Select	c.94G>C	p.Ala32Pro	missense	Exon 2 of 3	NP_002183.1	A4D1W7
	INHBA-AS1	NR_027118.2		n.170+6193C>G		intron	N/A
	INHBA-AS1	NR_027119.2		n.170+6193C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBA	ENST00000242208.5	TSL:1 MANE Select	c.94G>C	p.Ala32Pro	missense	Exon 2 of 3	ENSP00000242208.4	P08476
	INHBA	ENST00000442711.1	TSL:1	c.94G>C	p.Ala32Pro	missense	Exon 1 of 2	ENSP00000397197.1	P08476
	INHBA-AS1	ENST00000415848.6	TSL:1	n.173+6193C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443024 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 715290

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000302 AC: 1 AN: 33096

American (AMR) AF: 0.00 AC: 0 AN: 43760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.00 AC: 0 AN: 84110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100738

Other (OTH) AF: 0.00 AC: 0 AN: 59510

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.5
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.22
Sift	Benign	0.19	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.22		Gain of catalytic residue at A32 (P = 0.0161)
MVP		0.84
MPC		0.93
ClinPred		0.32	T
GERP RS		3.6
PromoterAI		0.024	Neutral
Varity_R		0.12
gMVP		0.39
Mutation Taster		=81/19	polymorphism

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: rs376838491; hg19: chr7-41739879;