rs6582484

Variant names:

• chr12-43796827-T-A
• rs6582484
• NM_002822.5:c.882+149A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-43796827-T-A
• chr12-43796827-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002822.5(TWF1):​c.882+149A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TWF1 NM_002822.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353
• Publications: 10 publications found

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]

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]

TMEM117 (HGNC:25308): (transmembrane protein 117) Involved in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Located in endoplasmic reticulum and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TWF1	NM_002822.5	c.882+149A>T		intron_variant	Intron 8 of 8	ENST00000395510.7	NP_002813.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TWF1	ENST00000395510.7	c.882+149A>T		intron_variant	Intron 8 of 8	1	NM_002822.5	ENSP00000378886.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 617702 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 324990

African (AFR) AF: 0.00 AC: 0 AN: 14734

American (AMR) AF: 0.00 AC: 0 AN: 18980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15780

East Asian (EAS) AF: 0.00 AC: 0 AN: 30992

South Asian (SAS) AF: 0.00 AC: 0 AN: 49420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 414442

Other (OTH) AF: 0.00 AC: 0 AN: 30956

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3513

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.55
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6582484; hg19: chr12-44190630;