Genetic Variant CLBA1:p.Ser258Gly (chr14-104993020-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S258C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CLBA1
NM_174891.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0740

Publications

0 publications found

Variant links:

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]

CLBA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041870296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174891.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLBA1	NM_174891.4	MANE Select	c.772A>G	p.Ser258Gly	missense	Exon 4 of 5	NP_777551.2	Q96F83
	CLBA1	NM_001364170.1		c.772A>G	p.Ser258Gly	missense	Exon 4 of 5	NP_001351099.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLBA1	ENST00000547315.6	TSL:1 MANE Select	c.772A>G	p.Ser258Gly	missense	Exon 4 of 5	ENSP00000450114.1	Q96F83
CLBA1	ENST00000550614.5	TSL:1	c.46A>G	p.Ser16Gly	missense	Exon 3 of 4	ENSP00000448642.1	J3KRA4
CLBA1	ENST00000548641.5	TSL:1	n.*200A>G		non_coding_transcript_exon	Exon 4 of 5	ENSP00000447892.1	F8VUA8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111996

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.52

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.036

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.33

M_CAP

Benign

0.0031

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

PhyloP100

-0.074

PROVEAN

Benign

-1.3

REVEL

Benign

0.022

Sift

Benign

0.59

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.12

MutPred

0.22

Gain of loop (P = 0.0851)

MVP

0.055

MPC

0.10

ClinPred

0.059

GERP RS

0.72

Varity_R

0.038

gMVP

0.047

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over