chr10-96227509-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_013314.4(BLNK):c.262G>A(p.Ala88Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,614,202 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A88S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0068 ( 11 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 10 hom. )

Consequence

BLNK
NM_013314.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.38

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062735677).

BP6

Variant 10-96227509-C-T is Benign according to our data. Variant chr10-96227509-C-T is described in ClinVar as [Benign]. Clinvar id is 487218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0068 (1036/152366) while in subpopulation AFR AF = 0.0222 (925/41590). AF 95% confidence interval is 0.0211. There are 11 homozygotes in GnomAd4. There are 501 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLNK	NM_013314.4 link	c.262G>A	p.Ala88Thr	missense_variant	Exon 5 of 17	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.262G>A	p.Ala88Thr	missense_variant	Exon 5 of 17	1	NM_013314.4	ENSP00000224337.6		Q8WV28-1

Frequencies

GnomAD3 genomes

AF:

0.00680

AC:

1036

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0223

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00764

GnomAD2 exomes

AF:

0.00175

AC:

439

AN:

251412

AF XY:

0.00129

show subpopulations

Gnomad AFR exome

AF:

0.0223

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000681

AC:

996

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000580

AC XY:

422

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0221

AC:

739

AN:

33480

Gnomad4 AMR exome

AF:

0.00228

AC:

102

AN:

44724

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0000927

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53366

Gnomad4 NFE exome

AF:

0.0000504

AC:

AN:

1112008

Gnomad4 Remaining exome

AF:

0.00132

AC:

AN:

60396

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00680

AC:

1036

AN:

152366

Hom.:

Cov.:

AF XY:

0.00672

AC XY:

501

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0222

AC:

0.0222409

AN:

0.0222409

Gnomad4 AMR

AF:

0.00536

AC:

0.00535808

AN:

0.00535808

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000207

AC:

0.000207039

AN:

0.000207039

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000176

AC:

0.000176372

AN:

0.000176372

Gnomad4 OTH

AF:

0.00756

AC:

0.00756144

AN:

0.00756144

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00238

Hom.:

Bravo

AF:

0.00805

ESP6500AA

AF:

0.0266

AC:

117

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00215

AC:

261

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Agammaglobulinemia 4, autosomal recessive

Benign:1

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;.;T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.092

FATHMM_MKL

Benign

0.10

LIST_S2

Uncertain

0.88

D;D;T;D

MetaRNN

Benign

0.0063

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;.;L

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.9

N;N;N;D

REVEL

Benign

0.074

Sift

Uncertain

0.022

D;D;D;D

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.64

P;P;B;.

Vest4

0.33

MVP

0.50

MPC

0.54

ClinPred

0.020

GERP RS

5.8

Varity_R

0.065

gMVP

0.094

Mutation Taster

=94/6

polymorphism

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