rs12051548

Variant names:

• chr17-4779740-G-C
• rs12051548
• NM_003963.3:c.178-1049G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003963.3(TM4SF5):​c.178-1049G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 152,230 control chromosomes in the GnomAD database, including 976 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 0.081 (976 hom., cov: 32)
• Consequence: TM4SF5 NM_003963.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 13 publications found

Genes affected

TM4SF5 (HGNC:11857): (transmembrane 4 L six family member 5) 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 and is highly similar in sequence and structure to transmembrane 4 superfamily member 1. It may play a role in cell proliferation, and overexpression of this protein may be associated with the uncontrolled growth of tumour cells. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TM4SF5	NM_003963.3	c.178-1049G>C		intron_variant	Intron 1 of 4	ENST00000270560.4	NP_003954.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TM4SF5	ENST00000270560.4	c.178-1049G>C		intron_variant	Intron 1 of 4	1	NM_003963.3	ENSP00000270560.3
TM4SF5	ENST00000576530.2	n.217-1049G>C		intron_variant	Intron 1 of 3	1

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12385 AN: 152112 Hom.: 974 Cov.: 32

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0802

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0798

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

GnomAD4 genome AF: 0.0815 AC: 12400 AN: 152230 Hom.: 976 Cov.: 32 AF XY: 0.0926 AC XY: 6890 AN XY: 74420

African (AFR) AF: 0.0613 AC: 2547 AN: 41556

American (AMR) AF: 0.0772 AC: 1179 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0802 AC: 278 AN: 3468

East Asian (EAS) AF: 0.380 AC: 1963 AN: 5172

South Asian (SAS) AF: 0.331 AC: 1597 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1617 AN: 10602

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3007 AN: 68016

Other (OTH) AF: 0.0814 AC: 172 AN: 2114

Alfa AF: 0.0599 Hom.: 48

Bravo AF: 0.0731

Asia WGS AF: 0.354 AC: 1230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-0.23
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: rs12051548; hg19: chr17-4683035;