4-10491263-C-G

Position:

• chr4-10491263-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052964.4(CLNK):​c.1141-650G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,136 control chromosomes in the GnomAD database, including 40,334 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 0.72 (40334 hom., cov: 32)
• Consequence: CLNK NM_052964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLNK	NM_052964.4	c.1141-650G>C		intron_variant		ENST00000226951.11
LOC105374482	XR_925387.4	n.83+2068C>G		intron_variant, non_coding_transcript_variant
CLNK	XM_011513775.3	c.1186-650G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLNK	ENST00000226951.11	c.1141-650G>C		intron_variant		1	NM_052964.4	P1
	ENST00000663264.1	n.96+34423C>G		intron_variant, non_coding_transcript_variant
CLNK	ENST00000515667.5	c.355-650G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110046 AN: 152018 Hom.: 40320 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.724 AC: 110098 AN: 152136 Hom.: 40334 Cov.: 32 AF XY: 0.722 AC XY: 53731 AN XY: 74380

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.730

Alfa AF: 0.700 Hom.: 2433

Bravo AF: 0.715

Asia WGS AF: 0.632 AC: 2200 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	1.4
DANN	Benign	0.67

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: rs9291420; hg19: chr4-10492887;