Genetic Variant NM_017935.5:c.68C>T (chr4-101790948-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017935.5(BANK1):c.68C>T(p.Pro23Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 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: 0.0000015 ( 0 hom. )

Consequence

BANK1
NM_017935.5 missense, splice_region

Scores

Splicing: ADA: 0.2191

Clinical Significance

Not reported in ClinVar

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=0.25131726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5 link	c.68C>T	p.Pro23Leu	missense_variant, splice_region_variant	Exon 1 of 17	ENST00000322953.9	NP_060405.5	Q8NDB2-1
BANK1	NM_001127507.3 link	c.68C>T	p.Pro23Leu	missense_variant, splice_region_variant	Exon 1 of 16		NP_001120979.3	Q8NDB2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BANK1	ENST00000322953.9 link	c.68C>T	p.Pro23Leu	missense_variant, splice_region_variant	Exon 1 of 17	1	NM_017935.5	ENSP00000320509.4	Q8NDB2-1
BANK1	ENST00000508653.5 link	c.68C>T	p.Pro23Leu	missense_variant, splice_region_variant	Exon 1 of 15	1		ENSP00000422314.1	Q8NDB2-4
BANK1	ENST00000428908.5 link	c.68C>T	p.Pro23Leu	missense_variant, splice_region_variant	Exon 1 of 16	5		ENSP00000412748.1	Q8NDB2-4
BANK1	ENST00000504592.5 link	c.26-38860C>T		intron_variant	Intron 5 of 20	2		ENSP00000421443.1	Q8NDB2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000147

AC:

AN:

1363482

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

671692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.35e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.70

T;T;.

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.9

L;L;L

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.089

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.0090

D;T;T

Polyphen

0.94

P;D;D

Vest4

0.21

MutPred

0.34

Loss of disorder (P = 0.0093);Loss of disorder (P = 0.0093);Loss of disorder (P = 0.0093);

MVP

0.51

MPC

0.026

ClinPred

0.94

GERP RS

0.74

Varity_R

0.063

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.22

dbscSNV1_RF

Benign

0.46

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over