2-219572359-C-T

Variant names:

• chr2-219572359-C-T
• rs35118453
• NM_002191.4:c.-16C>T

Variant summary

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

The NM_002191.4(INHA):​c.-16C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,613,276 control chromosomes in the GnomAD database, including 32,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (2677 hom., cov: 33)
  • Exomes 𝑓: 0.20 (30127 hom.)
• Consequence: INHA NM_002191.4 5_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.694
• Publications: 32 publications found

Genes affected

INHA (HGNC:6065): (inhibin subunit alpha) This gene encodes a member of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate multiple peptide products, including the alpha subunit of the inhibin A and B protein complexes. These complexes negatively regulate follicle stimulating hormone secretion from the pituitary gland. Inhibins have also been implicated in regulating numerous cellular processes including cell proliferation, apoptosis, immune response and hormone secretion. Mutations in this gene may be associated with male infertility and premature ovarian failure in female human patients. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002191.4. 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
	INHA	NM_002191.4	MANE Select	c.-16C>T		5_prime_UTR	Exon 1 of 2	NP_002182.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INHA	ENST00000243786.3	TSL:1 MANE Select	c.-16C>T		5_prime_UTR	Exon 1 of 2	ENSP00000243786.2
	INHA	ENST00000489456.1	TSL:2	n.286-2335C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27837 AN: 152050 Hom.: 2680 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.190 AC: 47742 AN: 251360 AF XY: 0.185

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.197

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.200 AC: 291695 AN: 1461108 Hom.: 30127 Cov.: 35 AF XY: 0.196 AC XY: 142304 AN XY: 726856

African (AFR) AF: 0.134 AC: 4482 AN: 33458

American (AMR) AF: 0.253 AC: 11337 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4453 AN: 26136

East Asian (EAS) AF: 0.169 AC: 6713 AN: 39700

South Asian (SAS) AF: 0.0943 AC: 8127 AN: 86198

European-Finnish (FIN) AF: 0.197 AC: 10507 AN: 53412

Middle Eastern (MID) AF: 0.163 AC: 856 AN: 5262

European-Non Finnish (NFE) AF: 0.210 AC: 233714 AN: 1111888

Other (OTH) AF: 0.191 AC: 11506 AN: 60330

GnomAD4 genome AF: 0.183 AC: 27842 AN: 152168 Hom.: 2677 Cov.: 33 AF XY: 0.182 AC XY: 13553 AN XY: 74414

African (AFR) AF: 0.134 AC: 5560 AN: 41526

American (AMR) AF: 0.240 AC: 3666 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3472

East Asian (EAS) AF: 0.194 AC: 1000 AN: 5166

South Asian (SAS) AF: 0.0924 AC: 446 AN: 4828

European-Finnish (FIN) AF: 0.196 AC: 2079 AN: 10596

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13834 AN: 67968

Other (OTH) AF: 0.182 AC: 383 AN: 2110

Alfa AF: 0.191 Hom.: 762

Bravo AF: 0.187

Asia WGS AF: 0.127 AC: 441 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		0.69
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs35118453; hg19: chr2-220437081; COSMIC: COSV54727885; COSMIC: COSV54727885;