rs9793

chr3-149474777-A-G

Variant summary

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

The NM_004617.4(TM4SF4):c.-101A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,254,594 control chromosomes in the GnomAD database, including 373,206 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 0.64 (34918 hom., cov: 32)
  • Exomes 𝑓: 0.77 (338288 hom.)
• Consequence: TM4SF4 NM_004617.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TM4SF4	NM_004617.4	c.-101A>G		5_prime_UTR_variant	1/5	ENST00000305354.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM4SF4	ENST00000305354.5	c.-101A>G		5_prime_UTR_variant	1/5	1	NM_004617.4	P1
TM4SF4	ENST00000465758.1	c.-101A>G		5_prime_UTR_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97090 AN: 151974 Hom.: 34922 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.0935

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.679

GnomAD4 exome AF: 0.765 AC: 843919 AN: 1102500 Hom.: 338288 Cov.: 14 AF XY: 0.760 AC XY: 413601 AN XY: 544318

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.663

Gnomad4 ASJ exome AF: 0.716

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.737

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.638 AC: 97103 AN: 152094 Hom.: 34918 Cov.: 32 AF XY: 0.629 AC XY: 46800 AN XY: 74356

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.0933

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.672

Alfa AF: 0.787 Hom.: 45445

Bravo AF: 0.628

Asia WGS AF: 0.281 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.0
Dann	Benign	0.67

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: rs9793; hg19: chr3-149192564; COSMIC: COSV59517488; COSMIC: COSV59517488;