4-10725733-T-C

Variant names:

• chr4-10725733-T-C
• rs13142500
• ENST00000720792.1:n.165-8868T>C

Variant summary

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

The ENST00000720792.1(LINC02498):​n.165-8868T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,500 control chromosomes in the GnomAD database, including 15,086 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 0.44 (15086 hom., cov: 29)
• Consequence: LINC02498 ENST00000720792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 19 publications found

Genes affected

LINC02498 (HGNC:53483): (long intergenic non-protein coding RNA 2498)

CLNK (HGNC:17438): (cytokine dependent hematopoietic cell linker) MIST is a member of the SLP76 family of adaptors (see LCP2, MIM 601603; BLNK, MIM 604515). MIST plays a role in the regulation of immunoreceptor signaling, including PLC-gamma (PLCG1; MIM 172420)-mediated B cell antigen receptor (BCR) signaling and FC-epsilon R1 (see FCER1A, MIM 147140)-mediated mast cell degranulation (Cao et al., 1999 [PubMed 10562326]; Goitsuka et al., 2000, 2001 [PubMed 10744659] [PubMed 11463797]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLNK	XM_011513775.3	c.3+8795A>G		intron_variant	Intron 1 of 18		XP_011512077.1
CLNK	XM_017007684.2	c.3+8795A>G		intron_variant	Intron 1 of 18		XP_016863173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC02498	ENST00000720792.1	n.165-8868T>C		intron_variant	Intron 1 of 2
LINC02498	ENST00000720793.1	n.66-8868T>C		intron_variant	Intron 1 of 2
LINC02498	ENST00000720794.1	n.142-8868T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66391 AN: 151380 Hom.: 15077 Cov.: 29

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.438 AC: 66419 AN: 151500 Hom.: 15086 Cov.: 29 AF XY: 0.446 AC XY: 33002 AN XY: 73998

African (AFR) AF: 0.325 AC: 13435 AN: 41314

American (AMR) AF: 0.529 AC: 8051 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1681 AN: 3454

East Asian (EAS) AF: 0.586 AC: 2999 AN: 5116

South Asian (SAS) AF: 0.486 AC: 2334 AN: 4800

European-Finnish (FIN) AF: 0.508 AC: 5327 AN: 10486

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31018 AN: 67790

Other (OTH) AF: 0.438 AC: 922 AN: 2106

Alfa AF: 0.146 Hom.: 889

Bravo AF: 0.438

Asia WGS AF: 0.476 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.30
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs13142500; hg19: chr4-10727357;