chr4-102022839-A-C

Variant names:

• chr4-102022839-A-C
• rs2850390
• NM_017935.5:c.1285+1247A>C

Variant summary

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

The NM_017935.5(BANK1):​c.1285+1247A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,006 control chromosomes in the GnomAD database, including 36,254 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 0.68 (36254 hom., cov: 32)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940
• Publications: 8 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

ENSG00000251309 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.1285+1247A>C		intron_variant	Intron 8 of 16	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.1195+1247A>C		intron_variant	Intron 8 of 16		NP_001077376.3
BANK1	NM_001127507.3	c.886+1247A>C		intron_variant	Intron 7 of 15		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.1285+1247A>C		intron_variant	Intron 8 of 16	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103456 AN: 151886 Hom.: 36228 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.681 AC: 103534 AN: 152006 Hom.: 36254 Cov.: 32 AF XY: 0.675 AC XY: 50181 AN XY: 74294

African (AFR) AF: 0.850 AC: 35268 AN: 41494

American (AMR) AF: 0.700 AC: 10680 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2244 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3196 AN: 5160

South Asian (SAS) AF: 0.645 AC: 3107 AN: 4814

European-Finnish (FIN) AF: 0.514 AC: 5425 AN: 10552

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41295 AN: 67940

Other (OTH) AF: 0.706 AC: 1490 AN: 2110

Alfa AF: 0.632 Hom.: 39587

Bravo AF: 0.702

Asia WGS AF: 0.669 AC: 2330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.77
PhyloP100		-0.94
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: rs2850390; hg19: chr4-102943996;