rs256962

Positions:

• chr5-115607014-A-G

Variant summary

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

The NM_001164468.4(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 NM_001164468.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TMED7-TICAM2	NM_001164468.4	c.566+9304T>C		intron_variant			NP_001157940.1
TMED7-TICAM2	NM_001164469.4	c.566+9304T>C		intron_variant			NP_001157941.1
TICAM2-AS1	NR_109874.1	n.417+3858A>G		intron_variant
TICAM2-AS1	NR_109875.1	n.417+3858A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMED7-TICAM2	ENST00000282382.8	c.566+9304T>C		intron_variant		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

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.460

Alfa AF: 0.498 Hom.: 25226

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

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: rs256962; hg19: chr5-114942711; COSMIC: COSV56696368; COSMIC: COSV56696368;