NM_052964.4:c.603-2637T>C

Variant names:

• chr4-10534920-A-G
• rs10488948
• NM_052964.4:c.603-2637T>C

Variant summary

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

The NM_052964.4(CLNK):​c.603-2637T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,970 control chromosomes in the GnomAD database, including 32,776 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 0.64 (32776 hom., cov: 31)
• Consequence: CLNK NM_052964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 6 publications found

Genes affected

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLNK	NM_052964.4	c.603-2637T>C		intron_variant	Intron 11 of 18	ENST00000226951.11	NP_443196.2
CLNK	XM_011513775.3	c.648-2637T>C		intron_variant	Intron 11 of 18		XP_011512077.1
CLNK	XM_017007684.2	c.648-2637T>C		intron_variant	Intron 11 of 18		XP_016863173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLNK	ENST00000226951.11	c.603-2637T>C		intron_variant	Intron 11 of 18	1	NM_052964.4	ENSP00000226951.6
CLNK	ENST00000507719.1	c.477-2637T>C		intron_variant	Intron 11 of 12	1		ENSP00000427208.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97737 AN: 151852 Hom.: 32743 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.644 AC: 97821 AN: 151970 Hom.: 32776 Cov.: 31 AF XY: 0.641 AC XY: 47613 AN XY: 74292

African (AFR) AF: 0.447 AC: 18498 AN: 41426

American (AMR) AF: 0.669 AC: 10199 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2569 AN: 3472

East Asian (EAS) AF: 0.634 AC: 3272 AN: 5164

South Asian (SAS) AF: 0.609 AC: 2927 AN: 4806

European-Finnish (FIN) AF: 0.688 AC: 7260 AN: 10550

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50818 AN: 67976

Other (OTH) AF: 0.678 AC: 1434 AN: 2114

Alfa AF: 0.692 Hom.: 14210

Bravo AF: 0.635

Asia WGS AF: 0.626 AC: 2177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.29
PhyloP100		-0.022
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: rs10488948; hg19: chr4-10536544;