rs7618915

Positions:

• chr3-52245578-G-A
• chr3-52245578-G-C
• chr3-52245578-G-T

Variant summary

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

The ENST00000679296.1(TWF2):​c.-270+1101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,784 control chromosomes in the GnomAD database, including 7,247 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 0.30 (7247 hom., cov: 31)
• Consequence: TWF2 ENST00000679296.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384

Genes affected

TWF2 (HGNC:9621): (twinfilin actin binding protein 2) The protein encoded by this gene was identified by its interaction with the catalytic domain of protein kinase C-zeta. The encoded protein contains an actin-binding site and an ATP-binding site. It is most closely related to twinfilin (PTK9), a conserved actin monomer-binding protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TWF2	ENST00000679296.1	c.-270+1101C>T		intron_variant				ENSP00000504576

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46180 AN: 151668 Hom.: 7243 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.304 AC: 46209 AN: 151784 Hom.: 7247 Cov.: 31 AF XY: 0.305 AC XY: 22609 AN XY: 74166

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.302

Alfa AF: 0.333 Hom.: 11969

Bravo AF: 0.299

Asia WGS AF: 0.330 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7618915; hg19: chr3-52279594;