8-11494403-C-T

Variant names:

• chr8-11494403-C-T
• rs922483
• NM_001715.3:c.-190C>T

Variant summary

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

The NM_001715.3(BLK):​c.-190C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,170 control chromosomes in the GnomAD database, including 8,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8896 hom., cov: 32)
  • Exomes 𝑓: 0.28 (2 hom.)
• Consequence: BLK NM_001715.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.38
• Publications: 58 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: Unknown, AD Classification: LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• 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=-0.74).
• BP6: Variant 8-11494403-C-T is Benign according to our data. Variant chr8-11494403-C-T is described in ClinVar as Benign. ClinVar VariationId is 361468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 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.-190C>T		5_prime_UTR	Exon 1 of 13	NP_001706.2
	BLK	NM_001330465.2		c.-279C>T		5_prime_UTR	Exon 1 of 12	NP_001317394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLK	ENST00000259089.9	TSL:1 MANE Select	c.-190C>T		5_prime_UTR	Exon 1 of 13	ENSP00000259089.4	P51451
	BLK	ENST00000525389.1	TSL:1	n.235C>T		non_coding_transcript_exon	Exon 1 of 2
	BLK	ENST00000645242.1		n.274+7236C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48852 AN: 151988 Hom.: 8879 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.281 AC: 18 AN: 64 Hom.: 2 Cov.: 0 AF XY: 0.283 AC XY: 13 AN XY: 46

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.241 AC: 13 AN: 54

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.322 AC: 48904 AN: 152106 Hom.: 8896 Cov.: 32 AF XY: 0.329 AC XY: 24465 AN XY: 74342

African (AFR) AF: 0.260 AC: 10768 AN: 41492

American (AMR) AF: 0.494 AC: 7559 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 807 AN: 3472

East Asian (EAS) AF: 0.720 AC: 3712 AN: 5156

South Asian (SAS) AF: 0.418 AC: 2013 AN: 4818

European-Finnish (FIN) AF: 0.304 AC: 3220 AN: 10576

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19758 AN: 67978

Other (OTH) AF: 0.329 AC: 696 AN: 2114

Alfa AF: 0.319 Hom.: 9019

Bravo AF: 0.339

Asia WGS AF: 0.584 AC: 2030 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		1.4
PromoterAI		0.030	Neutral
Mutation Taster		=298/2	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: rs922483; hg19: chr8-11351912;