4-10627462-T-C

Variant names:

• chr4-10627462-T-C
• rs2531204
• NM_052964.4:c.12-29413A>G

Variant summary

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

The NM_052964.4(CLNK):​c.12-29413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 152,266 control chromosomes in the GnomAD database, including 70,220 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 0.96 (70220 hom., cov: 31)
• Consequence: CLNK NM_052964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 1 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]

LOC105374480 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052964.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLNK	NM_052964.4	MANE Select	c.12-29413A>G		intron	N/A	NP_443196.2	Q7Z7G1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLNK	ENST00000226951.11	TSL:1 MANE Select	c.12-29413A>G		intron	N/A	ENSP00000226951.6	Q7Z7G1-1
	CLNK	ENST00000507719.1	TSL:1	c.-116+8315A>G		intron	N/A	ENSP00000427208.1	Q7Z7G1-2

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145923 AN: 152148 Hom.: 70182 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.967

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

GnomAD4 genome AF: 0.959 AC: 146019 AN: 152266 Hom.: 70220 Cov.: 31 AF XY: 0.960 AC XY: 71428 AN XY: 74442

African (AFR) AF: 0.880 AC: 36521 AN: 41522

American (AMR) AF: 0.978 AC: 14956 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3443 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5170

South Asian (SAS) AF: 0.973 AC: 4692 AN: 4824

European-Finnish (FIN) AF: 0.997 AC: 10584 AN: 10616

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.991 AC: 67411 AN: 68046

Other (OTH) AF: 0.968 AC: 2043 AN: 2110

Alfa AF: 0.985 Hom.: 12466

Bravo AF: 0.954

Asia WGS AF: 0.978 AC: 3401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.68
DANN	Benign	0.50
PhyloP100		-0.42
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: rs2531204; hg19: chr4-10629086;