rs10516486

Positions:

• chr4-101830119-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017935.5(BANK1):​c.382C>T​(p.Leu128Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,610,998 control chromosomes in the GnomAD database, including 138,341 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (19556 hom., cov: 32)
  • Exomes 𝑓: 0.40 (118785 hom.)
• Consequence: BANK1 NM_017935.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

Genes affected

BANK1 (HGNC:18233): (B cell scaffold protein with ankyrin repeats 1) The protein encoded by this gene is a B-cell-specific scaffold protein that functions in B-cell receptor-induced calcium mobilization from intracellular stores. This protein can also promote Lyn-mediated tyrosine phosphorylation of inositol 1,4,5-trisphosphate receptors. Polymorphisms in this gene are associated with susceptibility to systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=0.026 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANK1	NM_017935.5	c.382C>T	p.Leu128Leu	synonymous_variant	2/17	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.292C>T	p.Leu98Leu	synonymous_variant	2/17		NP_001077376.3
BANK1	NM_001127507.3	c.71-24916C>T		intron_variant			NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.382C>T	p.Leu128Leu	synonymous_variant	2/17	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73835 AN: 151948 Hom.: 19518 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.466

GnomAD3 exomes AF: 0.428 AC: 106137 AN: 248068 Hom.: 23716 AF XY: 0.420 AC XY: 56406 AN XY: 134270

Gnomad AFR exome AF: 0.715

Gnomad AMR exome AF: 0.448

Gnomad ASJ exome AF: 0.475

Gnomad EAS exome AF: 0.475

Gnomad SAS exome AF: 0.443

Gnomad FIN exome AF: 0.383

Gnomad NFE exome AF: 0.375

Gnomad OTH exome AF: 0.408

GnomAD4 exome AF: 0.399 AC: 581622 AN: 1458932 Hom.: 118785 Cov.: 34 AF XY: 0.399 AC XY: 289725 AN XY: 725660

Gnomad4 AFR exome AF: 0.711

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.437

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.486 AC: 73926 AN: 152066 Hom.: 19556 Cov.: 32 AF XY: 0.488 AC XY: 36252 AN XY: 74324

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.470

Alfa AF: 0.418 Hom.: 15081

Bravo AF: 0.498

Asia WGS AF: 0.525 AC: 1823 AN: 3474

EpiCase AF: 0.386

EpiControl AF: 0.387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10516486; hg19: chr4-102751276; COSMIC: COSV59839554;