NM_145200.5:c.15G>C

Variant names:

• chr11-67455438-G-C
• rs772573693
• NM_145200.5:c.15G>C

Variant summary

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

The NM_145200.5(CABP4):​c.15G>C​(p.Gln5His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CABP4 NM_145200.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

Genes affected

CABP4 (HGNC:1386): (calcium binding protein 4) This gene encodes a member of the CABP family of calcium binding protein characterized by four EF-hand motifs. Mutations in this gene are associated with congenital stationary night blindness type 2B. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

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=0.14689451).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABP4	NM_145200.5	c.15G>C	p.Gln5His	missense_variant	Exon 1 of 6	ENST00000325656.7	NP_660201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABP4	ENST00000325656.7	c.15G>C	p.Gln5His	missense_variant	Exon 1 of 6	1	NM_145200.5	ENSP00000324960.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000411 AC: 1 AN: 243046 Hom.: 0 AF XY: 0.00000752 AC XY: 1 AN XY: 133028

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: 0.0000331

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.86e-7 AC: 1 AN: 1458578 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725450

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.24
Sift	Benign	0.13	T
Sift4G	Benign	0.10	T
Polyphen		0.88	P
Vest4		0.28
MutPred		0.049		Gain of glycosylation at T3 (P = 0.054);
MVP		0.80
MPC		0.21
ClinPred		0.16	T
GERP RS		1.5
Varity_R		0.046
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs772573693; hg19: chr11-67222909;