10-96242781-T-A

Variant names:

• chr10-96242781-T-A
• NM_013314.4:c.117A>T
• BLNK p.Leu39Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_013314.4(BLNK):​c.117A>T​(p.Leu39Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L39L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BLNK NM_013314.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.497
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• agammaglobulinemia 4, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-0.497 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013314.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLNK	NM_013314.4	MANE Select	c.117A>T	p.Leu39Leu	synonymous	Exon 3 of 17	NP_037446.1	Q8WV28-1
	BLNK	NM_001114094.2		c.117A>T	p.Leu39Leu	synonymous	Exon 3 of 16	NP_001107566.1	Q8WV28-2
	BLNK	NM_001258440.2		c.117A>T	p.Leu39Leu	synonymous	Exon 3 of 16	NP_001245369.1	Q8WV28-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLNK	ENST00000224337.10	TSL:1 MANE Select	c.117A>T	p.Leu39Leu	synonymous	Exon 3 of 17	ENSP00000224337.6	Q8WV28-1
	BLNK	ENST00000371176.7	TSL:1	c.117A>T	p.Leu39Leu	synonymous	Exon 3 of 16	ENSP00000360218.2	Q8WV28-2
	BLNK	ENST00000413476.6	TSL:1	c.117A>T	p.Leu39Leu	synonymous	Exon 3 of 16	ENSP00000397487.2	Q8WV28-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.1
DANN	Benign	0.76
PhyloP100		-0.50

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-98002537;