rs17111459

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013314.4(BLNK):c.526-5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,612,622 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 68 hom. )

Consequence

BLNK
NM_013314.4 splice_region, intron

Scores

Splicing: ADA: 0.00002228

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.188

Variant links:

Genes affected

BLNK (HGNC:14211): (B cell linker) This gene encodes a cytoplasmic linker or adaptor protein that plays a critical role in B cell development. This protein bridges B cell receptor-associated kinase activation with downstream signaling pathways, thereby affecting various biological functions. The phosphorylation of five tyrosine residues is necessary for this protein to nucleate distinct signaling effectors following B cell receptor activation. Mutations in this gene cause hypoglobulinemia and absent B cells, a disease in which the pro- to pre-B-cell transition is developmentally blocked. Deficiency in this protein has also been shown in some cases of pre-B acute lymphoblastic leukemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]

BLNK links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-96216739-C-G is Benign according to our data. Variant chr10-96216739-C-G is described in ClinVar as [Benign]. Clinvar id is 471481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-96216739-C-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1825/152176) while in subpopulation AFR AF= 0.024 (998/41526). AF 95% confidence interval is 0.0228. There are 22 homozygotes in gnomad4. There are 868 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLNK	NM_013314.4 link	c.526-5G>C		splice_region_variant, intron_variant	Intron 6 of 16	ENST00000224337.10	NP_037446.1	Q8WV28-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLNK	ENST00000224337.10 link	c.526-5G>C		splice_region_variant, intron_variant	Intron 6 of 16	1	NM_013314.4	ENSP00000224337.6		Q8WV28-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1820

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.00180

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00823

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00699

AC:

1755

AN:

251020

Hom.:

AF XY:

0.00705

AC XY:

957

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.00544

Gnomad ASJ exome

AF:

0.00656

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00507

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.00759

Gnomad OTH exome

AF:

0.00883

GnomAD4 exome

AF:

0.00713

AC:

10410

AN:

1460446

Hom.:

Cov.:

AF XY:

0.00722

AC XY:

5247

AN XY:

726652

show subpopulations

Gnomad4 AFR exome

AF:

0.0238

Gnomad4 AMR exome

AF:

0.00577

Gnomad4 ASJ exome

AF:

0.00567

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00536

Gnomad4 FIN exome

AF:

0.00247

Gnomad4 NFE exome

AF:

0.00722

Gnomad4 OTH exome

AF:

0.00816

GnomAD4 genome

AF:

0.0120

AC:

1825

AN:

152176

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

868

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0240

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00726

Gnomad4 FIN

AF:

0.00180

Gnomad4 NFE

AF:

0.00823

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00847

Hom.:

Bravo

AF:

0.0121

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Agammaglobulinemia 4, autosomal recessive

Benign:2

Jul 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

BLNK-related disorder

Benign:1

Jul 11, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.34

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over