chr4-101790948-C-A

Variant names:

• chr4-101790948-C-A
• rs781234477
• NM_017935.5:c.68C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017935.5(BANK1):​c.68C>A​(p.Pro23Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,363,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000081 (0 hom.)
• Consequence: BANK1 NM_017935.5 missense, splice_region
• Scores: Splicing: ADA: 0.00003787
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.221
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10893768).

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.68C>A	p.Pro23Gln	missense splice_region	Exon 1 of 17	NP_060405.5
	BANK1	NM_001127507.3		c.68C>A	p.Pro23Gln	missense splice_region	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.68C>A	p.Pro23Gln	missense splice_region	Exon 1 of 17	ENSP00000320509.4	Q8NDB2-1
	BANK1	ENST00000508653.5	TSL:1	c.68C>A	p.Pro23Gln	missense splice_region	Exon 1 of 15	ENSP00000422314.1	Q8NDB2-4
	BANK1	ENST00000428908.5	TSL:5	c.68C>A	p.Pro23Gln	missense splice_region	Exon 1 of 16	ENSP00000412748.1	Q8NDB2-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000982 AC: 11 AN: 111984 AF XY: 0.0000487

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000281

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000526

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000807 AC: 11 AN: 1363482 Hom.: 0 Cov.: 30 AF XY: 0.00000447 AC XY: 3 AN XY: 671692

African (AFR) AF: 0.00 AC: 0 AN: 29990

American (AMR) AF: 0.000216 AC: 7 AN: 32446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23392

East Asian (EAS) AF: 0.000113 AC: 4 AN: 35248

South Asian (SAS) AF: 0.00 AC: 0 AN: 75900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5060

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069814

Other (OTH) AF: 0.00 AC: 0 AN: 56756

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.22
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.022
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.010	D
Polyphen		0.13	B
Vest4		0.22
MutPred		0.29		Loss of glycosylation at P23 (P = 0.0101)
MVP		0.42
MPC		0.029
ClinPred		0.11	T
GERP RS		0.74
PromoterAI		0.12	Neutral
Varity_R		0.069
gMVP		0.18
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.10
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: rs781234477; hg19: chr4-102712105;