chr4-101866266-G-T

Variant names:

• chr4-101866266-G-T
• rs4698977
• NM_017935.5:c.763+3602G>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.763+3602G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,966 control chromosomes in the GnomAD database, including 9,371 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 0.35 (9371 hom., cov: 32)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.763+3602G>T		intron_variant	Intron 4 of 16	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.673+3602G>T		intron_variant	Intron 4 of 16		NP_001077376.3
BANK1	NM_001127507.3	c.364+3602G>T		intron_variant	Intron 3 of 15		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.763+3602G>T		intron_variant	Intron 4 of 16	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52430 AN: 151848 Hom.: 9373 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.345 AC: 52460 AN: 151966 Hom.: 9371 Cov.: 32 AF XY: 0.347 AC XY: 25776 AN XY: 74282

African (AFR) AF: 0.391 AC: 16203 AN: 41466

American (AMR) AF: 0.255 AC: 3899 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1216 AN: 3466

East Asian (EAS) AF: 0.204 AC: 1057 AN: 5178

South Asian (SAS) AF: 0.179 AC: 863 AN: 4816

European-Finnish (FIN) AF: 0.454 AC: 4780 AN: 10534

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23483 AN: 67922

Other (OTH) AF: 0.324 AC: 685 AN: 2112

Alfa AF: 0.334 Hom.: 4567

Bravo AF: 0.331

Asia WGS AF: 0.227 AC: 789 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-0.047
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: rs4698977; hg19: chr4-102787423;