rs1305635920

Variant names:

• chr14-104993020-A-G
• NM_174891.4:c.772A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-104993020-A-G
• chr14-104993020-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174891.4(CLBA1):​c.772A>G​(p.Ser258Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 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: 6.8e-7 (0 hom.)
• Consequence: CLBA1 NM_174891.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041870296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLBA1	NM_174891.4	c.772A>G	p.Ser258Gly	missense_variant	Exon 4 of 5	ENST00000547315.6	NP_777551.2
CLBA1	NM_001364170.1	c.772A>G	p.Ser258Gly	missense_variant	Exon 4 of 5		NP_001351099.1
CLBA1	XM_005267318.5	c.772A>G	p.Ser258Gly	missense_variant	Exon 4 of 5		XP_005267375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLBA1	ENST00000547315.6	c.772A>G	p.Ser258Gly	missense_variant	Exon 4 of 5	1	NM_174891.4	ENSP00000450114.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461798 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727194

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: 8.99e-7

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	0.073
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.52
DANN	Benign	0.31
DEOGEN2	Benign	0.036	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.33	T;.;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.042	T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.59	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.12
MutPred		0.22		Gain of loop (P = 0.0851);.;.;
MVP		0.055
MPC		0.10
ClinPred		0.059	T
GERP RS		0.72
Varity_R		0.038
gMVP		0.047

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr14-105459357;