chr4-10498807-T-C

Variant names:

• chr4-10498807-T-C
• rs17467273
• NM_052964.4:c.1140+2449A>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.1140+2449A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,164 control chromosomes in the GnomAD database, including 6,905 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 0.28 (6905 hom., cov: 33)
• Consequence: CLNK NM_052964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• 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]

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 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.1140+2449A>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.1140+2449A>G		intron	N/A	ENSP00000226951.6	Q7Z7G1-1
	CLNK	ENST00000515667.5	TSL:3	c.354+2449A>G		intron	N/A	ENSP00000427256.1	D6RJB9
	ENSG00000287154	ENST00000663264.1		n.97-31327T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42211 AN: 152046 Hom.: 6904 Cov.: 33

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.277 AC: 42212 AN: 152164 Hom.: 6905 Cov.: 33 AF XY: 0.272 AC XY: 20229 AN XY: 74382

African (AFR) AF: 0.120 AC: 4991 AN: 41532

American (AMR) AF: 0.236 AC: 3611 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1013 AN: 5176

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4816

European-Finnish (FIN) AF: 0.326 AC: 3446 AN: 10580

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25966 AN: 67990

Other (OTH) AF: 0.281 AC: 594 AN: 2112

Alfa AF: 0.347 Hom.: 40638

Bravo AF: 0.266

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.25
PhyloP100		-0.27
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: rs17467273; hg19: chr4-10500431;