rs8134378

Variant names:

• chr21-41521831-G-A
• rs8134378
• ENST00000454499.6:c.-57+8142C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-41521831-G-A
• chr21-41521831-G-T

Variant summary

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

The ENST00000454499.6(TMPRSS2):​c.-57+8142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,152 control chromosomes in the GnomAD database, including 1,208 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 0.12 (1208 hom., cov: 32)
• Consequence: TMPRSS2 ENST00000454499.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• Publications: 30 publications found

Genes affected

TMPRSS2 (HGNC:11876): (transmembrane serine protease 2) This gene encodes a protein that belongs to the serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Serine proteases are known to be involved in many physiological and pathological processes. This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. This protein also facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. Viruses found to use this protein for cell entry include Influenza virus and the human coronaviruses HCoV-229E, MERS-CoV, SARS-CoV and SARS-CoV-2 (COVID-19 virus). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2020]

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 (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS2	ENST00000454499.6	c.-57+8142C>T		intron_variant	Intron 2 of 14	1		ENSP00000389006.2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17536 AN: 152034 Hom.: 1208 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.115 AC: 17545 AN: 152152 Hom.: 1208 Cov.: 32 AF XY: 0.114 AC XY: 8443 AN XY: 74382

African (AFR) AF: 0.179 AC: 7440 AN: 41488

American (AMR) AF: 0.0625 AC: 956 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0796 AC: 384 AN: 4824

European-Finnish (FIN) AF: 0.110 AC: 1162 AN: 10572

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6801 AN: 68002

Other (OTH) AF: 0.112 AC: 236 AN: 2110

Alfa AF: 0.0842 Hom.: 287

Bravo AF: 0.115

Asia WGS AF: 0.0350 AC: 122 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	0.36
DANN	Benign	0.48
PhyloP100		-0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8134378; hg19: chr21-42893758;