chr4-10512944-C-T

Variant names:

• chr4-10512944-C-T
• rs2868942
• NM_052964.4:c.906+520G>A

Variant summary

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

The NM_052964.4(CLNK):​c.906+520G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,906 control chromosomes in the GnomAD database, including 7,898 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 0.32 (7898 hom., cov: 31)
• Consequence: CLNK NM_052964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 3 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]

ENSG00000287154 (HGNC:58732):

LOC105374482 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.362 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.906+520G>A		intron	N/A	NP_443196.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLNK	ENST00000226951.11	TSL:1 MANE Select	c.906+520G>A		intron	N/A	ENSP00000226951.6
	CLNK	ENST00000515667.5	TSL:3	c.120+520G>A		intron	N/A	ENSP00000427256.1
	ENSG00000287154	ENST00000663264.1		n.97-17190C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48822 AN: 151788 Hom.: 7901 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.321 AC: 48836 AN: 151906 Hom.: 7898 Cov.: 31 AF XY: 0.324 AC XY: 24019 AN XY: 74232

African (AFR) AF: 0.367 AC: 15184 AN: 41412

American (AMR) AF: 0.334 AC: 5099 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3470

East Asian (EAS) AF: 0.192 AC: 991 AN: 5164

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4816

European-Finnish (FIN) AF: 0.359 AC: 3784 AN: 10538

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20431 AN: 67940

Other (OTH) AF: 0.311 AC: 653 AN: 2098

Alfa AF: 0.268 Hom.: 1602

Bravo AF: 0.322

Asia WGS AF: 0.237 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.53
PhyloP100		-0.17
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: rs2868942; hg19: chr4-10514568;