12-43796827-T-C

Position:

• chr12-43796827-T-C

Variant summary

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

The NM_002822.5(TWF1):​c.882+149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 768,710 control chromosomes in the GnomAD database, including 12,746 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 0.22 (4465 hom., cov: 32)
  • Exomes 𝑓: 0.15 (8281 hom.)
• Consequence: TWF1 NM_002822.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353

Genes affected

TWF1 (HGNC:9620): (twinfilin actin binding protein 1) This gene encodes twinfilin, an actin monomer-binding protein conserved from yeast to mammals. Studies of the mouse counterpart suggest that this protein may be an actin monomer-binding protein, and its localization to cortical G-actin-rich structures may be regulated by the small GTPase RAC1. [provided by RefSeq, Jul 2008]

TMEM117 (HGNC:):

IRAK4 (HGNC:17967): (interleukin 1 receptor associated kinase 4) This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

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 (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TWF1	NM_002822.5	c.882+149A>G		intron_variant		ENST00000395510.7	NP_002813.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TWF1	ENST00000395510.7	c.882+149A>G		intron_variant		1	NM_002822.5	ENSP00000378886	P3

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32647 AN: 151760 Hom.: 4449 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.0440

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.154 AC: 94791 AN: 616832 Hom.: 8281 AF XY: 0.153 AC XY: 49649 AN XY: 324548

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.215 AC: 32703 AN: 151878 Hom.: 4465 Cov.: 32 AF XY: 0.210 AC XY: 15623 AN XY: 74256

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.229

Alfa AF: 0.168 Hom.: 2933

Bravo AF: 0.226

Asia WGS AF: 0.149 AC: 519 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	2.8
DANN	Benign	0.66

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: rs6582484; hg19: chr12-44190630;