rs11540858

chr10-96247049-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_013314.4(BLNK):c.48G>A(p.Arg16=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00686 in 1,598,140 control chromosomes in the GnomAD database, including 597 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 0.035 (307 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (290 hom.)
• Consequence: BLNK NM_013314.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.002921
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.82

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 10-96247049-C-T is Benign according to our data. Variant chr10-96247049-C-T is described in ClinVar as [Benign]. Clinvar id is 471480.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-96247049-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLNK	NM_013314.4	c.48G>A	p.Arg16=	splice_region_variant, synonymous_variant	2/17	ENST00000224337.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLNK	ENST00000224337.10	c.48G>A	p.Arg16=	splice_region_variant, synonymous_variant	2/17	1	NM_013314.4	P2

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5256 AN: 152080 Hom.: 307 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.0287

GnomAD3 exomes AF: 0.00958 AC: 2328 AN: 243120 Hom.: 123 AF XY: 0.00723 AC XY: 950 AN XY: 131336

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.00669

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00146

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000898

Gnomad OTH exome AF: 0.00559

GnomAD4 exome AF: 0.00395 AC: 5709 AN: 1445942 Hom.: 290 Cov.: 28 AF XY: 0.00354 AC XY: 2548 AN XY: 718854

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.00832

Gnomad4 ASJ exome AF: 0.000155

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00112

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000680

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.0346 AC: 5262 AN: 152198 Hom.: 307 Cov.: 33 AF XY: 0.0338 AC XY: 2518 AN XY: 74412

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000970

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.00643 Hom.: 61

Bravo AF: 0.0388

Asia WGS AF: 0.00924 AC: 33 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Agammaglobulinemia 4, autosomal recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	16
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0029
dbscSNV1_RF	Benign	0.17
SpliceAI score (max)		0.11		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: rs11540858; hg19: chr10-98006805;