rs6831297

Variant names:

• chr4-10735030-T-C
• rs6831297
• ENST00000720792.1:n.422+172T>C

Variant summary

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

The ENST00000720792.1(LINC02498):​n.422+172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,082 control chromosomes in the GnomAD database, including 11,475 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 0.36 (11475 hom., cov: 33)
• Consequence: LINC02498 ENST00000720792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLNK	XM_011513775.3	c.-500A>G		upstream_gene_variant			XP_011512077.1
CLNK	XM_017007684.2	c.-500A>G		upstream_gene_variant			XP_016863173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC02498	ENST00000720792.1	n.422+172T>C		intron_variant	Intron 2 of 2
LINC02498	ENST00000720793.1	n.323+172T>C		intron_variant	Intron 2 of 2
LINC02498	ENST00000720794.1	n.399+172T>C		intron_variant	Intron 2 of 2
LINC02498	ENST00000720795.1	n.298+172T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54272 AN: 151966 Hom.: 11430 Cov.: 33

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.357 AC: 54359 AN: 152082 Hom.: 11475 Cov.: 33 AF XY: 0.356 AC XY: 26475 AN XY: 74356

African (AFR) AF: 0.597 AC: 24738 AN: 41456

American (AMR) AF: 0.250 AC: 3819 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 796 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1775 AN: 5174

South Asian (SAS) AF: 0.326 AC: 1569 AN: 4818

European-Finnish (FIN) AF: 0.306 AC: 3240 AN: 10578

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17356 AN: 67978

Other (OTH) AF: 0.356 AC: 749 AN: 2106

Alfa AF: 0.308 Hom.: 1396

Bravo AF: 0.361

Asia WGS AF: 0.358 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs6831297; hg19: chr4-10736654;