Variant 10-50743009-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001321958.2(ASAH2B):c.-5C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

ASAH2B
NM_001321958.2 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.1566

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.418

Variant links:

Genes affected

ASAH2B (HGNC:23456): (N-acylsphingosine amidohydrolase 2B) Predicted to enable N-acylsphingosine amidohydrolase activity. Predicted to be involved in ceramide catabolic process; long-chain fatty acid biosynthetic process; and sphingosine biosynthetic process. Predicted to be active in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ASAH2B links:

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ACMG classification

Classification made for transcript

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=0.10947856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
ASAH2B	NM_001321958.2 link	c.-5C>T	5_prime_UTR_premature_start_codon_gain_variant	2/6	ENST00000647317.2	NP_001308887.1	P0C7U1-2
ASAH2B	NM_001321958.2 link	c.-5C>T	splice_region_variant	2/6	ENST00000647317.2	NP_001308887.1	P0C7U1-2
ASAH2B	NM_001321958.2 link	c.-5C>T	5_prime_UTR_variant	2/6	ENST00000647317.2	NP_001308887.1	P0C7U1-2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
ASAH2B	ENST00000647317 link	c.-5C>T	5_prime_UTR_premature_start_codon_gain_variant	2/6	NM_001321958.2	ENSP00000496089.1	P0C7U1-2
ASAH2B	ENST00000647317.2 link	c.-5C>T	splice_region_variant	2/6	NM_001321958.2	ENSP00000496089.1	P0C7U1-2
ASAH2B	ENST00000647317 link	c.-5C>T	5_prime_UTR_variant	2/6	NM_001321958.2	ENSP00000496089.1	P0C7U1-2

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

151714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

251488

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000344

AC:

503

AN:

1461802

Hom.:

Cov.:

AF XY:

0.000316

AC XY:

230

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000415

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.000237

AC:

AN:

151832

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000326

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.85C>T (p.R29C) alteration is located in exon 2 (coding exon 1) of the ASAH2B gene. This alteration results from a C to T substitution at nucleotide position 85, causing the arginine (R) at amino acid position 29 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-0.065

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.36

.;N

REVEL

Benign

0.20

Sift

Benign

0.12

.;T

Sift4G

Benign

0.076

.;T

Polyphen

1.0

D;D

Vest4

0.33

MVP

0.42

MPC

0.54

ClinPred

0.053

GERP RS

2.8

Varity_R

0.086

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.16

dbscSNV1_RF

Benign

0.19

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over