dbSNP rs77943970: ARSI:p.His223His (chr5-150298255-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001012301.4(ARSI):c.669C>T(p.His223His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 1,613,926 control chromosomes in the GnomAD database, including 1,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.037 ( 125 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1284 hom. )

Consequence

ARSI
NM_001012301.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.458

Variant links:

Genes affected

ARSI (HGNC:32521): (arylsulfatase family member I) This gene encodes a protein that belongs to a large family of sulfatases that hydrolyze sulfate esters and sulfamates. Members of this family play a role in several cellular processes, including hormone synthesis, cell signaling in development and degradation of macromolecules. The protein encoded by this gene is thought to be secreted, and to function in extracellular space. [provided by RefSeq, Jul 2016]

ARSI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 5-150298255-G-A is Benign according to our data. Variant chr5-150298255-G-A is described in ClinVar as [Benign]. Clinvar id is 465196.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.458 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0373 (5675/152304) while in subpopulation AMR AF= 0.0418 (640/15310). AF 95% confidence interval is 0.0403. There are 125 homozygotes in gnomad4. There are 2842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 125 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4 link	c.669C>T	p.His223His	synonymous_variant	Exon 2 of 2	ENST00000328668.8	NP_001012301.1	Q5FYB1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARSI	ENST00000328668.8 link	c.669C>T	p.His223His	synonymous_variant	Exon 2 of 2	1	NM_001012301.4	ENSP00000333395.7	Q5FYB1-1
ARSI	ENST00000515301.2 link	c.240C>T	p.His80His	synonymous_variant	Exon 2 of 2	4		ENSP00000426879.2	Q5FYB1-2
ARSI	ENST00000509146.1 link	c.240C>T	p.His80His	synonymous_variant	Exon 2 of 2	4		ENSP00000420955.1	D6RDH0

Frequencies

GnomAD3 genomes

AF:

0.0373

AC:

5672

AN:

152188

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0236

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0419

Gnomad ASJ

AF:

0.0651

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00765

Gnomad FIN

AF:

0.0747

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0416

Gnomad OTH

AF:

0.0444

GnomAD3 exomes

AF:

0.0366

AC:

9155

AN:

250462

Hom.:

226

AF XY:

0.0361

AC XY:

4891

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.0235

Gnomad AMR exome

AF:

0.0296

Gnomad ASJ exome

AF:

0.0688

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00761

Gnomad FIN exome

AF:

0.0760

Gnomad NFE exome

AF:

0.0436

Gnomad OTH exome

AF:

0.0434

GnomAD4 exome

AF:

0.0396

AC:

57937

AN:

1461622

Hom.:

1284

Cov.:

AF XY:

0.0387

AC XY:

28109

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0244

Gnomad4 AMR exome

AF:

0.0319

Gnomad4 ASJ exome

AF:

0.0678

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00852

Gnomad4 FIN exome

AF:

0.0739

Gnomad4 NFE exome

AF:

0.0420

Gnomad4 OTH exome

AF:

0.0388

GnomAD4 genome

AF:

0.0373

AC:

5675

AN:

152304

Hom.:

125

Cov.:

AF XY:

0.0382

AC XY:

2842

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0236

Gnomad4 AMR

AF:

0.0418

Gnomad4 ASJ

AF:

0.0651

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00766

Gnomad4 FIN

AF:

0.0747

Gnomad4 NFE

AF:

0.0416

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0419

Hom.:

Bravo

AF:

0.0363

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0413

EpiControl

AF:

0.0464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spastic paraplegia

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.9

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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