rs11770488

Positions:

• chr7-41693256-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002192.4(INHBA):​c.389-2714A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,026 control chromosomes in the GnomAD database, including 1,385 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 0.11 (1385 hom., cov: 32)
• Consequence: INHBA NM_002192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INHBA	NM_002192.4	c.389-2714A>T		intron_variant		ENST00000242208.5	NP_002183.1
INHBA	XM_017012174.2	c.389-2714A>T		intron_variant			XP_016867663.2
INHBA	XM_047420335.1	c.389-2714A>T		intron_variant			XP_047276291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INHBA	ENST00000242208.5	c.389-2714A>T		intron_variant		1	NM_002192.4	ENSP00000242208	P1
INHBA	ENST00000442711.1	c.389-2714A>T		intron_variant		1		ENSP00000397197	P1
INHBA	ENST00000638023.1	c.389-2714A>T		intron_variant		5		ENSP00000490646	P1
INHBA	ENST00000416150.1	n.52+12028A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16908 AN: 151910 Hom.: 1384 Cov.: 32

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0638

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.0953

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

GnomAD4 genome AF: 0.111 AC: 16905 AN: 152026 Hom.: 1385 Cov.: 32 AF XY: 0.111 AC XY: 8251 AN XY: 74300

Gnomad4 AFR AF: 0.0282

Gnomad4 AMR AF: 0.0718

Gnomad4 ASJ AF: 0.0698

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.134 Hom.: 217

Bravo AF: 0.0948

Asia WGS AF: 0.0330 AC: 116 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	9.2
DANN	Benign	0.74

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: rs11770488; hg19: chr7-41732854;