rs256962

Variant names:

• chr5-115607014-A-G
• rs256962
• ENST00000282382.8:c.566+9304T>C

Variant summary

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

The ENST00000282382.8(TMED7-TICAM2):​c.566+9304T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,884 control chromosomes in the GnomAD database, including 16,861 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 0.47 (16861 hom., cov: 32)
• Consequence: TMED7-TICAM2 ENST00000282382.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 9 publications found

Genes affected

TMED7-TICAM2 (HGNC:33945): (TMED7-TICAM2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring transmembrane emp24 protein transport domain containing 7 (TMED7) and toll-like receptor adaptor molecule 2 (TICAM2) genes. Alternative splicing results in multiple transcript variants, one of which encodes a fusion protein that shares sequence identity with the products of each individual gene. This fusion product functions to negatively regulate the adaptor MyD88-independent toll-like receptor 4 pathway. [provided by RefSeq, Nov 2010]

TICAM2-AS1 (HGNC:55575): (TICAM2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMED7-TICAM2	NM_001164468.4	c.566+9304T>C		intron_variant	Intron 3 of 3		NP_001157940.1
TMED7-TICAM2	NM_001164469.4	c.566+9304T>C		intron_variant	Intron 3 of 3		NP_001157941.1
TICAM2-AS1	NR_109874.1	n.417+3858A>G		intron_variant	Intron 2 of 3
TICAM2-AS1	NR_109875.1	n.417+3858A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMED7-TICAM2	ENST00000282382.8	c.566+9304T>C		intron_variant	Intron 3 of 3	2		ENSP00000282382.4

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71220 AN: 151766 Hom.: 16850 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.469 AC: 71269 AN: 151884 Hom.: 16861 Cov.: 32 AF XY: 0.470 AC XY: 34928 AN XY: 74260

African (AFR) AF: 0.404 AC: 16732 AN: 41404

American (AMR) AF: 0.426 AC: 6509 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1806 AN: 3464

East Asian (EAS) AF: 0.462 AC: 2390 AN: 5170

South Asian (SAS) AF: 0.471 AC: 2268 AN: 4814

European-Finnish (FIN) AF: 0.525 AC: 5552 AN: 10566

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.508 AC: 34468 AN: 67886

Other (OTH) AF: 0.460 AC: 972 AN: 2112

Alfa AF: 0.492 Hom.: 31067

Bravo AF: 0.455

Asia WGS AF: 0.407 AC: 1415 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.18
PhyloP100		-1.7
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: rs256962; hg19: chr5-114942711; COSMIC: COSV56696368; COSMIC: COSV56696368;