8-11561264-C-T

Variant names:

• chr8-11561264-C-T
• rs4841561
• NM_001715.3:c.1030-38C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001715.3(BLK):​c.1030-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,599,138 control chromosomes in the GnomAD database, including 127,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (13181 hom., cov: 33)
  • Exomes 𝑓: 0.38 (113873 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0220
• Publications: 11 publications found

Genes affected

BLK (HGNC:1057): (BLK proto-oncogene, Src family tyrosine kinase) This gene encodes a nonreceptor tyrosine-kinase of the src family of proto-oncogenes that are typically involved in cell proliferation and differentiation. The protein has a role in B-cell receptor signaling and B-cell development. The protein also stimulates insulin synthesis and secretion in response to glucose and enhances the expression of several pancreatic beta-cell transcription factors. [provided by RefSeq, Aug 2010]

BLK Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• maturity-onset diabetes of the young type 11

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

BLK-AS1 (HGNC:58190):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.076).
• BP6: Variant 8-11561264-C-T is Benign according to our data. Variant chr8-11561264-C-T is described in ClinVar as Benign. ClinVar VariationId is 1192426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001715.3. 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
	BLK	NM_001715.3	MANE Select	c.1030-38C>T		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.817-38C>T		intron	N/A	NP_001317394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000259089.9	TSL:1 MANE Select	c.1030-38C>T		intron	N/A	ENSP00000259089.4	P51451
	BLK	ENST00000526097.1	TSL:1	n.932C>T		non_coding_transcript_exon	Exon 1 of 3
	BLK	ENST00000855155.1		c.1030-38C>T		intron	N/A	ENSP00000525214.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60638 AN: 151914 Hom.: 13161 Cov.: 33

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.393

GnomAD2 exomes AF: 0.444 AC: 101057 AN: 227774 AF XY: 0.439

Gnomad AFR exome AF: 0.358

Gnomad AMR exome AF: 0.591

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.923

Gnomad FIN exome AF: 0.410

Gnomad NFE exome AF: 0.346

Gnomad OTH exome AF: 0.409

GnomAD4 exome AF: 0.383 AC: 554266 AN: 1447106 Hom.: 113873 Cov.: 37 AF XY: 0.383 AC XY: 275386 AN XY: 718498

African (AFR) AF: 0.356 AC: 11815 AN: 33154

American (AMR) AF: 0.583 AC: 24977 AN: 42834

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8404 AN: 25912

East Asian (EAS) AF: 0.919 AC: 35709 AN: 38836

South Asian (SAS) AF: 0.455 AC: 38159 AN: 83882

European-Finnish (FIN) AF: 0.408 AC: 21351 AN: 52348

Middle Eastern (MID) AF: 0.345 AC: 1985 AN: 5756

European-Non Finnish (NFE) AF: 0.351 AC: 387940 AN: 1104524

Other (OTH) AF: 0.400 AC: 23926 AN: 59860

GnomAD4 genome AF: 0.399 AC: 60699 AN: 152032 Hom.: 13181 Cov.: 33 AF XY: 0.409 AC XY: 30408 AN XY: 74312

African (AFR) AF: 0.361 AC: 14972 AN: 41488

American (AMR) AF: 0.503 AC: 7689 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1136 AN: 3468

East Asian (EAS) AF: 0.924 AC: 4761 AN: 5154

South Asian (SAS) AF: 0.468 AC: 2249 AN: 4802

European-Finnish (FIN) AF: 0.430 AC: 4545 AN: 10580

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23898 AN: 67932

Other (OTH) AF: 0.401 AC: 848 AN: 2116

Alfa AF: 0.356 Hom.: 1871

Bravo AF: 0.410

Asia WGS AF: 0.670 AC: 2328 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Maturity-onset diabetes of the young type 11 (1)
-	-	1	Systemic lupus erythematosus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Uncertain	1.0
PhyloP100		0.022
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: rs4841561; hg19: chr8-11418773;