4-101790905-G-A

Variant names:

• chr4-101790905-G-A
• rs766984744
• NM_017935.5:c.25G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017935.5(BANK1):​c.25G>A​(p.Gly9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,385,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: BANK1 NM_017935.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.286
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039137453).

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.25G>A	p.Gly9Arg	missense	Exon 1 of 17	NP_060405.5
	BANK1	NM_001127507.3		c.25G>A	p.Gly9Arg	missense	Exon 1 of 16	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.25G>A	p.Gly9Arg	missense	Exon 1 of 17	ENSP00000320509.4	Q8NDB2-1
	BANK1	ENST00000508653.5	TSL:1	c.25G>A	p.Gly9Arg	missense	Exon 1 of 15	ENSP00000422314.1	Q8NDB2-4
	BANK1	ENST00000428908.5	TSL:5	c.25G>A	p.Gly9Arg	missense	Exon 1 of 16	ENSP00000412748.1	Q8NDB2-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1385890 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 684090

African (AFR) AF: 0.00 AC: 0 AN: 31126

American (AMR) AF: 0.00 AC: 0 AN: 35848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24904

East Asian (EAS) AF: 0.00 AC: 0 AN: 35900

South Asian (SAS) AF: 0.00 AC: 0 AN: 79264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5144

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078766

Other (OTH) AF: 0.00 AC: 0 AN: 57748

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.6
DANN	Benign	0.81
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.29
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.0080
Sift	Benign	1.0	T
Sift4G	Benign	0.39	T
Polyphen		0.0040	B
Vest4		0.095
MutPred		0.11		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.072
MPC		0.032
ClinPred		0.027	T
GERP RS		0.62
PromoterAI		0.040	Neutral
Varity_R		0.024
gMVP		0.16
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs766984744; hg19: chr4-102712062;