rs17467273

chr4-10498807-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLNK	NM_052964.4	c.1140+2449A>G		intron_variant		ENST00000226951.11
LOC105374482	XR_925387.4	n.261+2252T>C		intron_variant, non_coding_transcript_variant
CLNK	XM_011513775.3	c.1185+2449A>G		intron_variant
CLNK	XM_017007684.2	c.1185+2449A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLNK	ENST00000226951.11	c.1140+2449A>G		intron_variant		1	NM_052964.4	P1
	ENST00000663264.1	n.97-31327T>C		intron_variant, non_coding_transcript_variant
CLNK	ENST00000515667.5	c.354+2449A>G		intron_variant		3

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

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.281

Alfa AF: 0.360 Hom.: 20429

Bravo AF: 0.266

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs17467273; hg19: chr4-10500431;