rs7075831

Variant names:

• chr10-96201199-G-T
• rs7075831
• NM_013314.4:c.935-141C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013314.4(BLNK):​c.935-141C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 741,534 control chromosomes in the GnomAD database, including 3,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (739 hom., cov: 33)
  • Exomes 𝑓: 0.090 (2944 hom.)
• Consequence: BLNK NM_013314.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.320
• Publications: 5 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]

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-96201199-G-T is Benign according to our data. Variant chr10-96201199-G-T is described in ClinVar as Benign. ClinVar VariationId is 1269653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLNK	NM_013314.4	c.935-141C>A		intron_variant	Intron 13 of 16	ENST00000224337.10	NP_037446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLNK	ENST00000224337.10	c.935-141C>A		intron_variant	Intron 13 of 16	1	NM_013314.4	ENSP00000224337.6

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14094 AN: 152082 Hom.: 742 Cov.: 33

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0915

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0725

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0899 AC: 52998 AN: 589334 Hom.: 2944 AF XY: 0.0923 AC XY: 28899 AN XY: 313146

African (AFR) AF: 0.0937 AC: 1467 AN: 15664

American (AMR) AF: 0.155 AC: 4558 AN: 29416

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2112 AN: 18528

East Asian (EAS) AF: 0.151 AC: 4869 AN: 32162

South Asian (SAS) AF: 0.150 AC: 8654 AN: 57514

European-Finnish (FIN) AF: 0.0904 AC: 3425 AN: 37890

Middle Eastern (MID) AF: 0.0737 AC: 224 AN: 3040

European-Non Finnish (NFE) AF: 0.0688 AC: 25049 AN: 364006

Other (OTH) AF: 0.0848 AC: 2640 AN: 31114

GnomAD4 genome AF: 0.0926 AC: 14093 AN: 152200 Hom.: 739 Cov.: 33 AF XY: 0.0952 AC XY: 7084 AN XY: 74424

African (AFR) AF: 0.0940 AC: 3904 AN: 41520

American (AMR) AF: 0.134 AC: 2048 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3468

East Asian (EAS) AF: 0.131 AC: 678 AN: 5182

South Asian (SAS) AF: 0.167 AC: 803 AN: 4816

European-Finnish (FIN) AF: 0.0915 AC: 970 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0726 AC: 4934 AN: 68006

Other (OTH) AF: 0.104 AC: 220 AN: 2112

Alfa AF: 0.0886 Hom.: 95

Bravo AF: 0.0944

Asia WGS AF: 0.126 AC: 436 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.31
PhyloP100		0.32
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: rs7075831; hg19: chr10-97960955; COSMIC: COSV56409668; COSMIC: COSV56409668;