4-102064693-C-T

Variant names:

• chr4-102064693-C-T
• rs1395306
• NM_017935.5:c.2212+1555C>T

Variant summary

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

The NM_017935.5(BANK1):​c.2212+1555C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,016 control chromosomes in the GnomAD database, including 26,353 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 0.59 (26353 hom., cov: 32)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017935.5. 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
	BANK1	NM_017935.5	MANE Select	c.2212+1555C>T		intron	N/A	NP_060405.5
	BANK1	NM_001083907.3		c.2122+1555C>T		intron	N/A	NP_001077376.3	Q8NDB2-3
	BANK1	NM_001127507.3		c.1813+1555C>T		intron	N/A	NP_001120979.3	Q8NDB2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANK1	ENST00000322953.9	TSL:1 MANE Select	c.2212+1555C>T		intron	N/A	ENSP00000320509.4	Q8NDB2-1
	BANK1	ENST00000508653.5	TSL:1	c.1813+1555C>T		intron	N/A	ENSP00000422314.1	Q8NDB2-4
	BANK1	ENST00000504592.5	TSL:2	c.2167+1555C>T		intron	N/A	ENSP00000421443.1	Q8NDB2-2

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89012 AN: 151898 Hom.: 26339 Cov.: 32

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.586 AC: 89069 AN: 152016 Hom.: 26353 Cov.: 32 AF XY: 0.579 AC XY: 43023 AN XY: 74284

African (AFR) AF: 0.622 AC: 25787 AN: 41460

American (AMR) AF: 0.611 AC: 9346 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2162 AN: 3472

East Asian (EAS) AF: 0.594 AC: 3062 AN: 5158

South Asian (SAS) AF: 0.614 AC: 2960 AN: 4820

European-Finnish (FIN) AF: 0.448 AC: 4728 AN: 10548

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38948 AN: 67958

Other (OTH) AF: 0.618 AC: 1303 AN: 2110

Alfa AF: 0.560 Hom.: 12393

Bravo AF: 0.599

Asia WGS AF: 0.605 AC: 2107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.1
DANN	Benign	0.39
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: rs1395306; hg19: chr4-102985850;