rs2250788

Variant names:

• chr8-11494547-A-G
• rs2250788
• ENST00000525389.1:n.379A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-11494547-A-G
• chr8-11494547-A-T

Variant summary

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

The ENST00000525389.1(BLK):​n.379A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,266 control chromosomes in the GnomAD database, including 51,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51503 hom., cov: 33)
  • Exomes 𝑓: 0.81 (15 hom.)
• Consequence: BLK ENST00000525389.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00
• Publications: 14 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-11494547-A-G is Benign according to our data. Variant chr8-11494547-A-G is described in ClinVar as Benign. ClinVar VariationId is 361471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525389.1. 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
	BLK	NM_001715.3	MANE Select	c.-46A>G		5_prime_UTR	Exon 1 of 13	NP_001706.2
	BLK	NM_001330465.2		c.-135A>G		5_prime_UTR	Exon 1 of 12	NP_001317394.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000525389.1	TSL:1	n.379A>G		non_coding_transcript_exon	Exon 1 of 2
	BLK	ENST00000259089.9	TSL:1 MANE Select	c.-46A>G		5_prime_UTR	Exon 1 of 13	ENSP00000259089.4
	BLK	ENST00000645242.1		n.274+7380A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124904 AN: 152108 Hom.: 51462 Cov.: 33

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.814

GnomAD4 exome AF: 0.810 AC: 34 AN: 42 Hom.: 15 Cov.: 0 AF XY: 0.861 AC XY: 31 AN XY: 36

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.824 AC: 28 AN: 34

Other (OTH) AF: 0.750 AC: 6 AN: 8

GnomAD4 genome AF: 0.821 AC: 125002 AN: 152224 Hom.: 51503 Cov.: 33 AF XY: 0.815 AC XY: 60632 AN XY: 74420

African (AFR) AF: 0.827 AC: 34331 AN: 41534

American (AMR) AF: 0.863 AC: 13209 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2882 AN: 3472

East Asian (EAS) AF: 0.736 AC: 3816 AN: 5184

South Asian (SAS) AF: 0.796 AC: 3842 AN: 4826

European-Finnish (FIN) AF: 0.698 AC: 7386 AN: 10582

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.837 AC: 56952 AN: 68014

Other (OTH) AF: 0.817 AC: 1721 AN: 2106

Alfa AF: 0.842 Hom.: 24585

Bravo AF: 0.834

Asia WGS AF: 0.795 AC: 2765 AN: 3478

ClinVar

ClinVar submissions as Germline

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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.46
PhyloP100		0.0
PromoterAI		0.076	Neutral
Mutation Taster		=300/0	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: rs2250788; hg19: chr8-11352056;