rs56185487

Variant names:

• chr8-11548114-G-A
• rs56185487
• NM_001715.3:c.258G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001715.3(BLK):​c.258G>A​(p.Gln86Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,613,184 control chromosomes in the GnomAD database, including 165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (81 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (84 hom.)
• Consequence: BLK NM_001715.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.586
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 8-11548114-G-A is Benign according to our data. Variant chr8-11548114-G-A is described in ClinVar as Benign. ClinVar VariationId is 128526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.586 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0605 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.258G>A	p.Gln86Gln	synonymous	Exon 4 of 13	NP_001706.2
	BLK	NM_001330465.2		c.45G>A	p.Gln15Gln	synonymous	Exon 3 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.258G>A	p.Gln86Gln	synonymous	Exon 4 of 13	ENSP00000259089.4	P51451
	BLK	ENST00000855155.1		c.258G>A	p.Gln86Gln	synonymous	Exon 4 of 13	ENSP00000525214.1
	BLK	ENST00000855156.1		c.258G>A	p.Gln86Gln	synonymous	Exon 3 of 12	ENSP00000525215.1

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2860 AN: 152062 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00616 AC: 1547 AN: 251326 AF XY: 0.00514

Gnomad AFR exome AF: 0.0648

Gnomad AMR exome AF: 0.00500

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00352 AC: 5144 AN: 1461004 Hom.: 84 Cov.: 31 AF XY: 0.00328 AC XY: 2387 AN XY: 726864

African (AFR) AF: 0.0618 AC: 2066 AN: 33456

American (AMR) AF: 0.00548 AC: 245 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00252 AC: 217 AN: 86224

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53388

Middle Eastern (MID) AF: 0.00464 AC: 24 AN: 5170

European-Non Finnish (NFE) AF: 0.00205 AC: 2276 AN: 1111884

Other (OTH) AF: 0.00514 AC: 310 AN: 60328

GnomAD4 genome AF: 0.0188 AC: 2861 AN: 152180 Hom.: 81 Cov.: 32 AF XY: 0.0177 AC XY: 1320 AN XY: 74404

African (AFR) AF: 0.0625 AC: 2593 AN: 41492

American (AMR) AF: 0.00667 AC: 102 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00191 AC: 130 AN: 68000

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.0104 Hom.: 26

Bravo AF: 0.0212

Asia WGS AF: 0.00433 AC: 16 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00196

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Maturity-onset diabetes of the young type 11 (2)
-	-	2	not specified (2)
-	-	1	Systemic lupus erythematosus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.8
DANN	Benign	0.59
PhyloP100		0.59
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: rs56185487; hg19: chr8-11405623;