7-41695436-C-T

Variant names:

• chr7-41695436-C-T
• rs2237432
• NM_002192.4:c.388+4551G>A

Variant summary

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

The NM_002192.4(INHBA):​c.388+4551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,098 control chromosomes in the GnomAD database, including 43,731 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 0.75 (43731 hom., cov: 32)
• Consequence: INHBA NM_002192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBA	NM_002192.4	MANE Select	c.388+4551G>A		intron	N/A	NP_002183.1
	INHBA-AS1	NR_027118.2		n.170+1348C>T		intron	N/A
	INHBA-AS1	NR_027119.2		n.170+1348C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHBA	ENST00000242208.5	TSL:1 MANE Select	c.388+4551G>A		intron	N/A	ENSP00000242208.4
	INHBA	ENST00000442711.1	TSL:1	c.388+4551G>A		intron	N/A	ENSP00000397197.1
	INHBA-AS1	ENST00000415848.6	TSL:1	n.173+1348C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114667 AN: 151980 Hom.: 43701 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.754 AC: 114742 AN: 152098 Hom.: 43731 Cov.: 32 AF XY: 0.754 AC XY: 56019 AN XY: 74344

African (AFR) AF: 0.807 AC: 33472 AN: 41480

American (AMR) AF: 0.614 AC: 9388 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2367 AN: 3472

East Asian (EAS) AF: 0.600 AC: 3091 AN: 5152

South Asian (SAS) AF: 0.704 AC: 3394 AN: 4822

European-Finnish (FIN) AF: 0.840 AC: 8886 AN: 10576

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51657 AN: 67992

Other (OTH) AF: 0.727 AC: 1534 AN: 2110

Alfa AF: 0.753 Hom.: 28661

Bravo AF: 0.734

Asia WGS AF: 0.678 AC: 2355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		0.40
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: rs2237432; hg19: chr7-41735034;