chr14-104986453-G-A

Variant names:

• chr14-104986453-G-A
• rs773962698
• NM_174891.4:c.22G>A

Variant summary

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

The NM_174891.4(CLBA1):​c.22G>A​(p.Gly8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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: 0.0000014 (0 hom.)
• Consequence: CLBA1 NM_174891.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912

Genes affected

CLBA1 (HGNC:20126): (clathrin binding box of aftiphilin containing 1) Predicted to enable clathrin binding activity. Predicted to be involved in intracellular transport. Predicted to be part of AP-1 adaptor complex. Predicted to be active in trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09157604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLBA1	NM_174891.4	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 5	ENST00000547315.6	NP_777551.2
CLBA1	NM_001364170.1	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 5		NP_001351099.1
CLBA1	XM_005267318.5	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 5		XP_005267375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLBA1	ENST00000547315.6	c.22G>A	p.Gly8Arg	missense_variant	Exon 1 of 5	1	NM_174891.4	ENSP00000450114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 247074 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134618

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460566 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726574

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.95
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.027
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		0.70	P
Vest4		0.076
MutPred		0.19		Gain of MoRF binding (P = 0.0068);
MVP		0.040
MPC		0.14
ClinPred		0.12	T
GERP RS		-0.98
Varity_R		0.056
gMVP		0.14

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: rs773962698; hg19: chr14-105452790;