rs4917723

Variant names:

• chr10-96222819-A-C
• rs4917723
• NM_013314.4:c.525+1007T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-96222819-A-C
• chr10-96222819-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013314.4(BLNK):​c.525+1007T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,076 control chromosomes in the GnomAD database, including 11,044 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (11044 hom., cov: 31)
• Consequence: BLNK NM_013314.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640
• Publications: 6 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• autosomal agammaglobulinemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLNK	NM_013314.4	MANE Select	c.525+1007T>G		intron	N/A	NP_037446.1
	BLNK	NM_001114094.2		c.525+1007T>G		intron	N/A	NP_001107566.1
	BLNK	NM_001258440.2		c.525+1007T>G		intron	N/A	NP_001245369.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLNK	ENST00000224337.10	TSL:1 MANE Select	c.525+1007T>G		intron	N/A	ENSP00000224337.6
	BLNK	ENST00000371176.7	TSL:1	c.525+1007T>G		intron	N/A	ENSP00000360218.2
	BLNK	ENST00000413476.6	TSL:1	c.525+1007T>G		intron	N/A	ENSP00000397487.2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56448 AN: 151956 Hom.: 11049 Cov.: 31

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.371 AC: 56447 AN: 152076 Hom.: 11044 Cov.: 31 AF XY: 0.379 AC XY: 28148 AN XY: 74328

African (AFR) AF: 0.254 AC: 10531 AN: 41476

American (AMR) AF: 0.390 AC: 5955 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3472

East Asian (EAS) AF: 0.323 AC: 1670 AN: 5174

South Asian (SAS) AF: 0.485 AC: 2333 AN: 4810

European-Finnish (FIN) AF: 0.519 AC: 5477 AN: 10562

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28030 AN: 67986

Other (OTH) AF: 0.363 AC: 765 AN: 2108

Alfa AF: 0.378 Hom.: 10721

Bravo AF: 0.351

Asia WGS AF: 0.364 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.3
DANN	Benign	0.71
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4917723; hg19: chr10-97982575;