rs12051548

Positions:

• chr17-4779740-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TM4SF5	NM_003963.3	c.178-1049G>C		intron_variant		ENST00000270560.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TM4SF5	ENST00000270560.4	c.178-1049G>C		intron_variant		1	NM_003963.3	P1
TM4SF5	ENST00000576530.2	n.217-1049G>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.0772

Gnomad4 ASJ AF: 0.0802

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0814

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

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: rs12051548; hg19: chr17-4683035;