3-149493600-C-T

Variant names:

• chr3-149493600-C-T
• rs9843304
• NM_004617.4:c.402-5122C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004617.4. 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
	TM4SF4	NM_004617.4	MANE Select	c.402-5122C>T		intron	N/A	NP_004608.1	P48230

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM4SF4	ENST00000305354.5	TSL:1 MANE Select	c.402-5122C>T		intron	N/A	ENSP00000305852.4	P48230
	TM4SF4	ENST00000865228.1		c.432-5122C>T		intron	N/A	ENSP00000535287.1
	TM4SF4	ENST00000463068.1	TSL:2	n.267-5122C>T		intron	N/A

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

African (AFR) AF: 0.158 AC: 6550 AN: 41492

American (AMR) AF: 0.546 AC: 8349 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1580 AN: 3470

East Asian (EAS) AF: 0.532 AC: 2749 AN: 5172

South Asian (SAS) AF: 0.578 AC: 2786 AN: 4822

European-Finnish (FIN) AF: 0.482 AC: 5096 AN: 10574

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37466 AN: 67972

Other (OTH) AF: 0.469 AC: 990 AN: 2110

Alfa AF: 0.504 Hom.: 53649

Bravo AF: 0.425

Asia WGS AF: 0.523 AC: 1819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.8
DANN	Benign	0.65
PhyloP100		0.0090
Mutation Taster		=100/0	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: rs9843304; hg19: chr3-149211387;