10-96192322-CTACT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013314.4(BLNK):c.1252-234_1252-231del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,152 control chromosomes in the GnomAD database, including 720 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.070 (720 hom., cov: 31)
• Consequence: BLNK NM_013314.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.663

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]

ZNF518A (HGNC:29009): (zinc finger protein 518A) The protein encoded by this gene is a member of the krueppel C2H2-type zinc finger protein family. The encoded protein contains five zinc fingers and is likely a nuclear transcriptional regulator. Numerous transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-96192322-CTACT-C is Benign according to our data. Variant chr10-96192322-CTACT-C is described in ClinVar as [Benign]. Clinvar id is 1224035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLNK	NM_013314.4	c.1252-234_1252-231del		intron_variant		ENST00000224337.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLNK	ENST00000224337.10	c.1252-234_1252-231del		intron_variant		1	NM_013314.4	P2

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10686 AN: 152034 Hom.: 722 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0320

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0762

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

GnomAD4 genome AF: 0.0702 AC: 10688 AN: 152152 Hom.: 720 Cov.: 31 AF XY: 0.0692 AC XY: 5149 AN XY: 74408

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0450

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0312

Gnomad4 FIN AF: 0.0171

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.0560 Hom.: 59

Bravo AF: 0.0772

Asia WGS AF: 0.0220 AC: 78 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs149157547; hg19: chr10-97952078;