chr4-68491213-G-A

Position:

• chr4-68491213-G-A

Variant summary

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

The NM_014058.4(TMPRSS11E):​c.1111-5430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 145,214 control chromosomes in the GnomAD database, including 8,761 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 0.33 (8761 hom., cov: 25)
• Consequence: TMPRSS11E NM_014058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS11E	NM_014058.4	c.1111-5430G>A		intron_variant		ENST00000305363.9
TMPRSS11E	XM_011531896.3	c.877-5430G>A		intron_variant
TMPRSS11E	XM_047450139.1	c.877-5430G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS11E	ENST00000305363.9	c.1111-5430G>A		intron_variant		1	NM_014058.4	P1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 47459 AN: 145106 Hom.: 8761 Cov.: 25

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.526

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.327 AC: 47459 AN: 145214 Hom.: 8761 Cov.: 25 AF XY: 0.321 AC XY: 22512 AN XY: 70118

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.369

Alfa AF: 0.385 Hom.: 3163

Bravo AF: 0.316

Asia WGS AF: 0.217 AC: 752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.68

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: rs35293564; hg19: chr4-69356931;