Variant 1-109229572-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_006513.4(SARS1):c.447G>A(p.Glu149=) variant causes a splice region, synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,608,314 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 25 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 28 hom. )

Consequence

SARS1
NM_006513.4 splice_region, synonymous

Scores

Splicing: ADA: 0.9995

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.93

Variant links:

Genes affected

SARS1 (HGNC:10537): (seryl-tRNA synthetase 1) This gene belongs to the class II amino-acyl tRNA family. The encoded enzyme catalyzes the transfer of L-serine to tRNA (Ser) and is related to bacterial and yeast counterparts. Multiple alternatively spliced transcript variants have been described but the biological validity of all variants is unknown. [provided by RefSeq, Jul 2010]

SARS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-109229572-G-A is Benign according to our data. Variant chr1-109229572-G-A is described in ClinVar as [Benign]. Clinvar id is 767683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00993 (1513/152318) while in subpopulation AFR AF= 0.0351 (1457/41562). AF 95% confidence interval is 0.0336. There are 25 homozygotes in gnomad4. There are 686 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SARS1	NM_006513.4 linkuse as main transcript	c.447G>A	p.Glu149=	splice_region_variant, synonymous_variant	4/11	ENST00000234677.7	NP_006504.2
SARS1	NM_001330669.1 linkuse as main transcript	c.447G>A	p.Glu149=	splice_region_variant, synonymous_variant	4/12		NP_001317598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SARS1	ENST00000234677.7 linkuse as main transcript	c.447G>A	p.Glu149=	splice_region_variant, synonymous_variant	4/11	1	NM_006513.4	ENSP00000234677	P1
SARS1	ENST00000369923.4 linkuse as main transcript	c.447G>A	p.Glu149=	splice_region_variant, synonymous_variant	4/12	5		ENSP00000358939
SARS1	ENST00000477544.5 linkuse as main transcript	n.472G>A		splice_region_variant, non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.00991

AC:

1509

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0351

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00253

AC:

627

AN:

247376

Hom.:

AF XY:

0.00193

AC XY:

258

AN XY:

133810

show subpopulations

Gnomad AFR exome

AF:

0.0358

Gnomad AMR exome

AF:

0.000788

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000365

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00103

AC:

1505

AN:

1455996

Hom.:

Cov.:

AF XY:

0.000876

AC XY:

634

AN XY:

723944

show subpopulations

Gnomad4 AFR exome

AF:

0.0376

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000386

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.00993

AC:

1513

AN:

152318

Hom.:

Cov.:

AF XY:

0.00921

AC XY:

686

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0351

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.96

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

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