Variant 10-96201199-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013314.4(BLNK):c.935-141C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 741,534 control chromosomes in the GnomAD database, including 3,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 739 hom., cov: 33)

Exomes 𝑓: 0.090 ( 2944 hom. )

Consequence

BLNK
NM_013314.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.320

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:

ZNF518A (HGNC:):

ZNF518A 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 10-96201199-G-T is Benign according to our data. Variant chr10-96201199-G-T is described in ClinVar as [Benign]. Clinvar id is 1269653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLNK	NM_013314.4 linkuse as main transcript	c.935-141C>A		intron_variant		ENST00000224337.10	NP_037446.1	Q8WV28-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLNK	ENST00000224337.10 linkuse as main transcript	c.935-141C>A		intron_variant		1	NM_013314.4	ENSP00000224337.6		Q8WV28-1

Frequencies

GnomAD3 genomes

AF:

0.0927

AC:

14094

AN:

152082

Hom.:

742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0941

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0915

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0725

Gnomad OTH

AF:

0.106

GnomAD4 exome

AF:

0.0899

AC:

52998

AN:

589334

Hom.:

2944

AF XY:

0.0923

AC XY:

28899

AN XY:

313146

show subpopulations

Gnomad4 AFR exome

AF:

0.0937

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.0904

Gnomad4 NFE exome

AF:

0.0688

Gnomad4 OTH exome

AF:

0.0848

GnomAD4 genome

AF:

0.0926

AC:

14093

AN:

152200

Hom.:

739

Cov.:

AF XY:

0.0952

AC XY:

7084

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0940

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.131

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.0915

Gnomad4 NFE

AF:

0.0726

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.0886

Hom.:

Bravo

AF:

0.0944

Asia WGS

AF:

0.126

AC:

436

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.7

DANN

Benign

0.31

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

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