4-68475319-T-C

Position:

• chr4-68475319-T-C

Variant summary

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

The NM_014058.4(TMPRSS11E):​c.529+558T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,832 control chromosomes in the GnomAD database, including 18,166 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 0.48 (18166 hom., cov: 30)
• Consequence: TMPRSS11E NM_014058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

Genes affected

TMPRSS11E (HGNC:24465): (transmembrane serine protease 11E) Predicted to enable serine-type peptidase activity. Involved in cognition. Predicted to be integral component of plasma membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS11E	NM_014058.4	c.529+558T>C		intron_variant		ENST00000305363.9	NP_054777.2
TMPRSS11E	XM_011531896.3	c.295+558T>C		intron_variant			XP_011530198.1
TMPRSS11E	XM_047450139.1	c.295+558T>C		intron_variant			XP_047306095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS11E	ENST00000305363.9	c.529+558T>C		intron_variant		1	NM_014058.4	ENSP00000307519	P1
TMPRSS11E	ENST00000510647.1	c.354+558T>C		intron_variant, NMD_transcript_variant		3		ENSP00000424109

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72849 AN: 151714 Hom.: 18146 Cov.: 30

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.480 AC: 72909 AN: 151832 Hom.: 18166 Cov.: 30 AF XY: 0.487 AC XY: 36096 AN XY: 74174

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.480

Alfa AF: 0.426 Hom.: 4895

Bravo AF: 0.481

Asia WGS AF: 0.610 AC: 2120 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.47

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: rs2708699; hg19: chr4-69341037;