Variant chr4-101790948-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANK1	NM_017935.5 linkuse as main transcript	c.68C>A	p.Pro23Gln	missense_variant, splice_region_variant	1/17	ENST00000322953.9	NP_060405.5	Q8NDB2-1
BANK1	NM_001127507.3 linkuse as main transcript	c.68C>A	p.Pro23Gln	missense_variant, splice_region_variant	1/16		NP_001120979.3	Q8NDB2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BANK1	ENST00000322953.9 linkuse as main transcript	c.68C>A	p.Pro23Gln	missense_variant, splice_region_variant	1/17	1	NM_017935.5	ENSP00000320509.4	Q8NDB2-1
BANK1	ENST00000508653.5 linkuse as main transcript	c.68C>A	p.Pro23Gln	missense_variant, splice_region_variant	1/15	1		ENSP00000422314.1	Q8NDB2-4
BANK1	ENST00000428908.5 linkuse as main transcript	c.68C>A	p.Pro23Gln	missense_variant, splice_region_variant	1/16	5		ENSP00000412748.1	Q8NDB2-4
BANK1	ENST00000504592.5 linkuse as main transcript	c.26-38860C>A		intron_variant		2		ENSP00000421443.1	Q8NDB2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000982

AC:

AN:

111984

Hom.:

AF XY:

0.0000487

AC XY:

AN XY:

61660

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000807

AC:

AN:

1363482

Hom.:

Cov.:

AF XY:

0.00000447

AC XY:

AN XY:

671692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000216

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000113

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 31, 2024

The c.68C>A (p.P23Q) alteration is located in exon 1 (coding exon 1) of the BANK1 gene. This alteration results from a C to A substitution at nucleotide position 68, causing the proline (P) at amino acid position 23 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.083

T;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.57

T;T;.

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;L

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.022

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.010

D;T;T

Polyphen

0.13

B;P;P

Vest4

0.22

MutPred

0.29

Loss of glycosylation at P23 (P = 0.0101);Loss of glycosylation at P23 (P = 0.0101);Loss of glycosylation at P23 (P = 0.0101);

MVP

0.42

MPC

0.029

ClinPred

0.11

GERP RS

0.74

Varity_R

0.069

gMVP

0.18

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over