chr4-101790948-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017935.5(BANK1):​c.68C>G​(p.Pro23Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 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: 0.000010 (0 hom.)
• Consequence: BANK1 NM_017935.5 missense, splice_region
• Scores: Splicing: ADA: 0.00008315
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

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]

ACMG classification

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=0.10017207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.68C>G	p.Pro23Arg	missense_variant, splice_region_variant	Exon 1 of 17	ENST00000322953.9	NP_060405.5
BANK1	NM_001127507.3	c.68C>G	p.Pro23Arg	missense_variant, splice_region_variant	Exon 1 of 16		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.68C>G	p.Pro23Arg	missense_variant, splice_region_variant	Exon 1 of 17	1	NM_017935.5	ENSP00000320509.4
BANK1	ENST00000508653.5	c.68C>G	p.Pro23Arg	missense_variant, splice_region_variant	Exon 1 of 15	1		ENSP00000422314.1
BANK1	ENST00000428908.5	c.68C>G	p.Pro23Arg	missense_variant, splice_region_variant	Exon 1 of 16	5		ENSP00000412748.1
BANK1	ENST00000504592.5	c.26-38860C>G		intron_variant	Intron 5 of 20	2		ENSP00000421443.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000893 AC: 1 AN: 111984 Hom.: 0 AF XY: 0.0000162 AC XY: 1 AN XY: 61660

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000539

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 14 AN: 1363482 Hom.: 0 Cov.: 30 AF XY: 0.0000119 AC XY: 8 AN XY: 671692

Gnomad4 AFR exome AF: 0.0000333

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000142

Gnomad4 SAS exome AF: 0.0000922

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000176

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000195 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T;.;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.52	T;T;.
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.078	T;D;D
Sift4G	Uncertain	0.011	D;T;T
Polyphen		0.033	B;B;B
Vest4		0.16
MutPred		0.28		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		0.41
MPC		0.022
ClinPred		0.32	T
GERP RS		0.74
Varity_R		0.051
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000083
dbscSNV1_RF	Benign	0.21
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs781234477; hg19: chr4-102712105;