Variant 22-50622771-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000487.6(ARSA):c.*2374C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 152,318 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 78 hom., cov: 32)

Exomes 𝑓: 0.053 ( 0 hom. )

Consequence

ARSA
NM_000487.6 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.236

Variant links:

Genes affected

ARSA (HGNC:713): (arylsulfatase A) The protein encoded by this gene hydrolyzes cerebroside sulfate to cerebroside and sulfate. Defects in this gene lead to metachromatic leucodystrophy (MLD), a progressive demyelination disease which results in a variety of neurological symptoms and ultimately death. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2010]

ARSA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 22-50622771-G-T is Benign according to our data. Variant chr22-50622771-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 342183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0272 (4139/152280) while in subpopulation NFE AF= 0.0386 (2623/68022). AF 95% confidence interval is 0.0373. There are 78 homozygotes in gnomad4. There are 2061 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 78 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSA	NM_000487.6 linkuse as main transcript	c.*2374C>A		3_prime_UTR_variant	8/8	ENST00000216124.10

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
ARSA	ENST00000216124.10 linkuse as main transcript	c.*2374C>A	3_prime_UTR_variant	8/8	1	NM_000487.6	P1
ARSA	ENST00000610191.1 linkuse as main transcript	n.556C>A	non_coding_transcript_exon_variant	1/1
ARSA	ENST00000608497.1 linkuse as main transcript	c.*350C>A	3_prime_UTR_variant, NMD_transcript_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

4141

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00659

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0210

Gnomad ASJ

AF:

0.0567

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0274

Gnomad FIN

AF:

0.0504

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0386

Gnomad OTH

AF:

0.0254

GnomAD4 exome

AF:

0.0526

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0833

AC XY:

AN XY:

show subpopulations

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.0385

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0272

AC:

4139

AN:

152280

Hom.:

Cov.:

AF XY:

0.0277

AC XY:

2061

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00657

Gnomad4 AMR

AF:

0.0210

Gnomad4 ASJ

AF:

0.0567

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0272

Gnomad4 FIN

AF:

0.0504

Gnomad4 NFE

AF:

0.0386

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0316

Hom.:

Bravo

AF:

0.0240

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Metachromatic leukodystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.8

DANN

Benign

0.86

Splicing

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