chr4-67963811-A-G

Variant names:

• chr4-67963811-A-G
• rs6552135
• ENST00000500538.7:n.1988-98796A>G

Variant summary

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

The ENST00000334830.11(TMPRSS11A):​c.-418T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 153,446 control chromosomes in the GnomAD database, including 15,672 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 0.40 (15456 hom., cov: 32)
  • Exomes 𝑓: 0.55 (216 hom.)
• Consequence: TMPRSS11A ENST00000334830.11 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 3 publications found

Genes affected

UBA6-DT (HGNC:49083): (UBA6 divergent transcript)

TMPRSS11A (HGNC:27954): (transmembrane serine protease 11A) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. Predicted to be integral component of plasma 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000334830.11. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA6-DT	ENST00000500538.7	TSL:1	n.1988-98796A>G		intron	N/A
	TMPRSS11A	ENST00000334830.11	TSL:2	c.-418T>C		5_prime_UTR	Exon 1 of 10	ENSP00000334611.7	A0A0A0MR82
	TMPRSS11A	ENST00000714501.1		c.-418T>C		5_prime_UTR	Exon 1 of 10	ENSP00000519753.1	A0AAQ5BIA6

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61244 AN: 151956 Hom.: 15462 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.547 AC: 750 AN: 1370 Hom.: 216 Cov.: 0 AF XY: 0.569 AC XY: 387 AN XY: 680

African (AFR) AF: 0.0714 AC: 4 AN: 56

American (AMR) AF: 0.333 AC: 8 AN: 24

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 30 AN: 76

East Asian (EAS) AF: 0.538 AC: 28 AN: 52

South Asian (SAS) AF: 0.500 AC: 6 AN: 12

European-Finnish (FIN) AF: 0.413 AC: 19 AN: 46

Middle Eastern (MID) AF: 0.333 AC: 2 AN: 6

European-Non Finnish (NFE) AF: 0.612 AC: 602 AN: 984

Other (OTH) AF: 0.447 AC: 51 AN: 114

GnomAD4 genome AF: 0.403 AC: 61240 AN: 152076 Hom.: 15456 Cov.: 32 AF XY: 0.398 AC XY: 29590 AN XY: 74320

African (AFR) AF: 0.103 AC: 4279 AN: 41530

American (AMR) AF: 0.385 AC: 5882 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 1569 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1997 AN: 5172

South Asian (SAS) AF: 0.421 AC: 2032 AN: 4824

European-Finnish (FIN) AF: 0.505 AC: 5319 AN: 10532

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38748 AN: 67958

Other (OTH) AF: 0.392 AC: 827 AN: 2110

Alfa AF: 0.493 Hom.: 2864

Bravo AF: 0.377

Asia WGS AF: 0.392 AC: 1352 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		2.2
PromoterAI		-0.0014	Neutral
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: rs6552135; hg19: chr4-68829529;