chr10-50743009-C-T

Variant names:

• chr10-50743009-C-T
• rs141006980
• NM_001321958.2:c.-5C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.10947856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321958.2. 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
	ASAH2B	NM_001321958.2	MANE Select	c.-5C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001308887.1	P0C7U1-2
	ASAH2B	NM_001321958.2	MANE Select	c.-5C>T		splice_region	Exon 2 of 6	NP_001308887.1	P0C7U1-2
	ASAH2B	NM_001321958.2	MANE Select	c.-5C>T		5_prime_UTR	Exon 2 of 6	NP_001308887.1	P0C7U1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH2B	ENST00000647317.2	MANE Select	c.-5C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000496089.1	P0C7U1-2
	ASAH2B	ENST00000647317.2	MANE Select	c.-5C>T		splice_region	Exon 2 of 6	ENSP00000496089.1	P0C7U1-2
	ASAH2B	ENST00000647317.2	MANE Select	c.-5C>T		5_prime_UTR	Exon 2 of 6	ENSP00000496089.1	P0C7U1-2

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 151714 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000143 AC: 36 AN: 251488 AF XY: 0.000162

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 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.: 0 Cov.: 31 AF XY: 0.000316 AC XY: 230 AN XY: 727214

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000415 AC: 461 AN: 1111936

Other (OTH) AF: 0.000546 AC: 33 AN: 60392

GnomAD4 genome AF: 0.000237 AC: 36 AN: 151832 Hom.: 0 Cov.: 32 AF XY: 0.000243 AC XY: 18 AN XY: 74192

African (AFR) AF: 0.0000966 AC: 4 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 67934

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000326 Hom.: 0

Bravo AF: 0.000223

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000763

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.065
Eigen_PC	Benign	-0.085
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.42
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.20
Sift	Benign	0.12	T
Sift4G	Benign	0.076	T
Polyphen		1.0	D
Vest4		0.33
MVP		0.42
MPC		0.54
ClinPred		0.053	T
GERP RS		2.8
Varity_R		0.086
gMVP		0.22
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs141006980; hg19: chr10-52502769;