rs727852

Variant names:

• chr10-96230827-A-C
• rs727852
• NM_013314.4:c.171T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-96230827-A-C
• chr10-96230827-A-G
• chr10-96230827-A-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS1

The NM_013314.4(BLNK):​c.171T>G​(p.Pro57Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,609,718 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P57P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: BLNK NM_013314.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 23 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.102 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000178 (26/1457730) while in subpopulation EAS AF = 0.000631 (25/39634). AF 95% confidence interval is 0.000438. There are 0 homozygotes in GnomAdExome4. There are 12 alleles in the male GnomAdExome4 subpopulation. Median coverage is 55. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLNK	NM_013314.4	c.171T>G	p.Pro57Pro	synonymous_variant	Exon 4 of 17	ENST00000224337.10	NP_037446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLNK	ENST00000224337.10	c.171T>G	p.Pro57Pro	synonymous_variant	Exon 4 of 17	1	NM_013314.4	ENSP00000224337.6

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151988 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000582

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000246 AC: 6 AN: 243678 AF XY: 0.0000228

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000333

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1457730 Hom.: 0 Cov.: 55 AF XY: 0.0000166 AC XY: 12 AN XY: 724536

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.000631 AC: 25 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 85148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110192

Other (OTH) AF: 0.0000166 AC: 1 AN: 60274

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151988 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74226

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 101224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.51
DANN	Benign	0.57
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs727852; hg19: chr10-97990583;