rs12386974

Variant names:

• chr8-11543119-C-G
• rs12386974
• NM_001715.3:c.-1-105C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-11543119-C-G
• chr8-11543119-C-A
• chr8-11543119-C-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.-1-105C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,577,420 control chromosomes in the GnomAD database, including 236,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25363 hom., cov: 32)
  • Exomes 𝑓: 0.53 (211141 hom.)
• Consequence: BLK NM_001715.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.165
• Publications: 6 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=-0.82).
• BP6: Variant 8-11543119-C-G is Benign according to our data. Variant chr8-11543119-C-G is described in ClinVar as Benign. ClinVar VariationId is 1192422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 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.-1-105C>G		intron	N/A	NP_001706.2
	BLK	NM_001330465.2		c.-90-2933C>G		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.-1-105C>G		intron	N/A	ENSP00000259089.4	P51451
	BLK	ENST00000855155.1		c.-1-105C>G		intron	N/A	ENSP00000525214.1
	BLK	ENST00000645242.1		n.275-2933C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86054 AN: 151970 Hom.: 25329 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.534 AC: 760882 AN: 1425332 Hom.: 211141 AF XY: 0.537 AC XY: 380549 AN XY: 708966

African (AFR) AF: 0.575 AC: 18894 AN: 32854

American (AMR) AF: 0.751 AC: 32422 AN: 43184

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 10518 AN: 25712

East Asian (EAS) AF: 0.998 AC: 39210 AN: 39294

South Asian (SAS) AF: 0.696 AC: 58648 AN: 84214

European-Finnish (FIN) AF: 0.594 AC: 26661 AN: 44888

Middle Eastern (MID) AF: 0.507 AC: 2482 AN: 4896

European-Non Finnish (NFE) AF: 0.495 AC: 540080 AN: 1091154

Other (OTH) AF: 0.541 AC: 31967 AN: 59136

GnomAD4 genome AF: 0.566 AC: 86139 AN: 152088 Hom.: 25363 Cov.: 32 AF XY: 0.580 AC XY: 43125 AN XY: 74362

African (AFR) AF: 0.575 AC: 23833 AN: 41470

American (AMR) AF: 0.664 AC: 10160 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1395 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5147 AN: 5174

South Asian (SAS) AF: 0.706 AC: 3397 AN: 4814

European-Finnish (FIN) AF: 0.631 AC: 6674 AN: 10574

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33605 AN: 67972

Other (OTH) AF: 0.562 AC: 1186 AN: 2112

Alfa AF: 0.372 Hom.: 950

Bravo AF: 0.574

Asia WGS AF: 0.828 AC: 2875 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	1.5
DANN	Benign	0.57
PhyloP100		-0.17
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: rs12386974; hg19: chr8-11400628;