10-50742980-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079516.4(ASAH2B):​c.56C>T​(p.Ser19Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,614,032 control chromosomes in the GnomAD database, including 434 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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. S19C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.032 (219 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (215 hom.)
• Consequence: ASAH2B NM_001079516.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014772117).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079516.4. 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
	ASAH2B	NM_001321958.2	MANE Select	c.-34C>T		5_prime_UTR	Exon 2 of 6	NP_001308887.1	P0C7U1-2
	ASAH2B	NM_001079516.4		c.56C>T	p.Ser19Phe	missense	Exon 2 of 6	NP_001072984.1	P0C7U1-1
	ASAH2B	NM_001321957.2		c.56C>T	p.Ser19Phe	missense	Exon 2 of 6	NP_001308886.1	P0C7U1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAH2B	ENST00000647317.2	MANE Select	c.-34C>T		5_prime_UTR	Exon 2 of 6	ENSP00000496089.1	P0C7U1-2
	ASAH2B	ENST00000374006.1	TSL:3	c.56C>T	p.Ser19Phe	missense	Exon 2 of 6	ENSP00000363118.1	P0C7U1-1
	ASAH2B	ENST00000643851.1		c.56C>T	p.Ser19Phe	missense	Exon 2 of 6	ENSP00000495463.1	P0C7U1-1

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 4814 AN: 152052 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0282

GnomAD2 exomes AF: 0.00898 AC: 2259 AN: 251484 AF XY: 0.00679

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00830

Gnomad ASJ exome AF: 0.00327

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00115

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.00370 AC: 5404 AN: 1461862 Hom.: 215 Cov.: 31 AF XY: 0.00334 AC XY: 2430 AN XY: 727232

African (AFR) AF: 0.106 AC: 3556 AN: 33478

American (AMR) AF: 0.00838 AC: 375 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00356 AC: 93 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00190 AC: 164 AN: 86258

European-Finnish (FIN) AF: 0.000168 AC: 9 AN: 53420

Middle Eastern (MID) AF: 0.0101 AC: 58 AN: 5768

European-Non Finnish (NFE) AF: 0.000596 AC: 663 AN: 1111984

Other (OTH) AF: 0.00805 AC: 486 AN: 60396

GnomAD4 genome AF: 0.0317 AC: 4829 AN: 152170 Hom.: 219 Cov.: 32 AF XY: 0.0309 AC XY: 2296 AN XY: 74400

African (AFR) AF: 0.106 AC: 4405 AN: 41498

American (AMR) AF: 0.0181 AC: 276 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4820

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000941 AC: 64 AN: 67998

Other (OTH) AF: 0.0279 AC: 59 AN: 2112

Alfa AF: 0.0101 Hom.: 24

Bravo AF: 0.0369

ESP6500AA AF: 0.107 AC: 473

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.0106 AC: 1286

EpiCase AF: 0.00109

EpiControl AF: 0.00160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.19
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.081
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.023	D
Polyphen		0.0	B
Vest4		0.098
MPC		1.1
ClinPred		0.040	T
GERP RS		-3.7
Varity_R		0.059
gMVP		0.16
Mutation Taster		=93/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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;