chr10-50742980-C-G

Variant names:

• chr10-50742980-C-G
• rs75066720
• NM_001321958.2:c.-34C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001321958.2(ASAH2B):​c.-34C>G 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 0.00000137 in 1,461,864 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ASAH2B NM_001321958.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.188
• Publications: 1 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05509463).

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.-34C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001308887.1	P0C7U1-2
	ASAH2B	NM_001321958.2	MANE Select	c.-34C>G		5_prime_UTR	Exon 2 of 6	NP_001308887.1	P0C7U1-2
	ASAH2B	NM_001321959.2		c.-34C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001308888.1	P0C7U1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH2B	ENST00000647317.2	MANE Select	c.-34C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000496089.1	P0C7U1-2
	ASAH2B	ENST00000647317.2	MANE Select	c.-34C>G		5_prime_UTR	Exon 2 of 6	ENSP00000496089.1	P0C7U1-2
	ASAH2B	ENST00000374007.5	TSL:3	c.-34C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000363119.1	P0C7U1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251484 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111984

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

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	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.88
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.19
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Benign	0.032	D
Sift4G	Uncertain	0.027	D
Polyphen		0.0	B
Vest4		0.18
MutPred		0.46		Loss of helix (P = 0.0072)
MVP		0.014
MPC		1.1
ClinPred		0.21	T
GERP RS		-3.7
Varity_R		0.082
gMVP		0.19
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs75066720; hg19: chr10-52502740;