4-101848520-G-A

Variant names:

• chr4-101848520-G-A
• rs12498977
• NM_017935.5:c.470-6515G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017935.5(BANK1):​c.470-6515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 152,078 control chromosomes in the GnomAD database, including 795 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 0.079 (795 hom., cov: 33)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 5 publications found

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]

BANK1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.470-6515G>A		intron_variant	Intron 2 of 16	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.380-6515G>A		intron_variant	Intron 2 of 16		NP_001077376.3
BANK1	NM_001127507.3	c.71-6515G>A		intron_variant	Intron 1 of 15		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.470-6515G>A		intron_variant	Intron 2 of 16	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11959 AN: 151960 Hom.: 793 Cov.: 33

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0788 AC: 11979 AN: 152078 Hom.: 795 Cov.: 33 AF XY: 0.0832 AC XY: 6186 AN XY: 74316

African (AFR) AF: 0.0288 AC: 1194 AN: 41500

American (AMR) AF: 0.207 AC: 3159 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1195 AN: 5168

South Asian (SAS) AF: 0.100 AC: 484 AN: 4822

European-Finnish (FIN) AF: 0.0539 AC: 568 AN: 10536

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0693 AC: 4710 AN: 68000

Other (OTH) AF: 0.105 AC: 222 AN: 2110

Alfa AF: 0.0689 Hom.: 257

Bravo AF: 0.0881

Asia WGS AF: 0.148 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.44
PhyloP100		1.1
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: rs12498977; hg19: chr4-102769677;