chr11-118082245-A-G

Variant names:

• chr11-118082245-A-G
• rs12279572
• NM_019894.4:c.3+4940A>G

Variant summary

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

The NM_019894.4(TMPRSS4):​c.3+4940A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,078 control chromosomes in the GnomAD database, including 4,662 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 0.25 (4662 hom., cov: 32)
• Consequence: TMPRSS4 NM_019894.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 1 publications found

Genes affected

TMPRSS4 (HGNC:11878): (transmembrane serine protease 4) This gene encodes a member of the serine protease family. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified as a gene overexpressed in pancreatic carcinoma. The encoded protein is membrane bound with a N-terminal anchor sequence and a glycosylated extracellular region containing the serine protease domain. The protein has been found to promote SARS-CoV-2 entry into host cells. [provided by RefSeq, Aug 2021]

SMIM35 (HGNC:44179): (small integral membrane protein 35) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS4	NM_019894.4	c.3+4940A>G		intron_variant	Intron 1 of 12	ENST00000437212.8	NP_063947.2
SMIM35	NM_001394165.1	c.7+4506T>C		intron_variant	Intron 1 of 4	ENST00000689828.1	NP_001381094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS4	ENST00000437212.8	c.3+4940A>G		intron_variant	Intron 1 of 12	1	NM_019894.4	ENSP00000416037.3
SMIM35	ENST00000689828.1	c.7+4506T>C		intron_variant	Intron 1 of 4		NM_001394165.1	ENSP00000509259.1
TMPRSS4	ENST00000522824.5	c.3+4940A>G		intron_variant	Intron 1 of 12	1		ENSP00000430547.1
TMPRSS4	ENST00000714375.1	n.3+4940A>G		intron_variant	Intron 1 of 11			ENSP00000519642.1
TMPRSS4	ENST00000714378.1	n.3+4940A>G		intron_variant	Intron 1 of 13			ENSP00000519645.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37421 AN: 151960 Hom.: 4659 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.246 AC: 37426 AN: 152078 Hom.: 4662 Cov.: 32 AF XY: 0.247 AC XY: 18388 AN XY: 74342

African (AFR) AF: 0.193 AC: 8008 AN: 41478

American (AMR) AF: 0.285 AC: 4360 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3470

East Asian (EAS) AF: 0.181 AC: 938 AN: 5182

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4818

European-Finnish (FIN) AF: 0.226 AC: 2386 AN: 10578

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18498 AN: 67964

Other (OTH) AF: 0.268 AC: 565 AN: 2108

Alfa AF: 0.256 Hom.: 815

Bravo AF: 0.245

Asia WGS AF: 0.232 AC: 808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.72
PhyloP100		-1.6
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: rs12279572; hg19: chr11-117952960;