3-149493600-C-T

Variant summary

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

The NM_004617.4(TM4SF4):c.402-5122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,100 control chromosomes in the GnomAD database, including 16,658 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 0.43 (16658 hom., cov: 33)
• Consequence: TM4SF4 NM_004617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

Genes affected

TM4SF4 (HGNC:11856): (transmembrane 4 L six family member 4) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that can regulate cell proliferation.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TM4SF4	NM_004617.4	c.402-5122C>T		intron_variant		ENST00000305354.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM4SF4	ENST00000305354.5	c.402-5122C>T		intron_variant		1	NM_004617.4	P1
TM4SF4	ENST00000463068.1	n.267-5122C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66100 AN: 151982 Hom.: 16652 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.435 AC: 66126 AN: 152100 Hom.: 16658 Cov.: 33 AF XY: 0.434 AC XY: 32279 AN XY: 74354

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.469

Alfa AF: 0.530 Hom.: 34938

Bravo AF: 0.425

Asia WGS AF: 0.523 AC: 1819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.8
Dann	Benign	0.65

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: rs9843304; hg19: chr3-149211387;