1-109236555-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_006513.4(SARS1):​c.1257+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,597,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

SARS1
NM_006513.4 splice_region, intron

Scores

2
Splicing: ADA: 0.0001148
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.320
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 1-109236555-G-A is Benign according to our data. Variant chr1-109236555-G-A is described in ClinVar as [Benign]. Clinvar id is 732354.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000604 (92/152240) while in subpopulation AFR AF= 0.00219 (91/41556). AF 95% confidence interval is 0.00183. There are 0 homozygotes in gnomad4. There are 46 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SARS1NM_006513.4 linkc.1257+7G>A splice_region_variant, intron_variant Intron 9 of 10 ENST00000234677.7 NP_006504.2 P49591Q0VGA5
SARS1NM_001330669.1 linkc.1257+7G>A splice_region_variant, intron_variant Intron 9 of 11 NP_001317598.1 Q5T5C7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SARS1ENST00000234677.7 linkc.1257+7G>A splice_region_variant, intron_variant Intron 9 of 10 1 NM_006513.4 ENSP00000234677.2 P49591
SARS1ENST00000369923.4 linkc.1257+7G>A splice_region_variant, intron_variant Intron 9 of 11 5 ENSP00000358939.4 Q5T5C7
SARS1ENST00000468588.1 linkn.325G>A non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.000605
AC:
92
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00220
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000183
AC:
46
AN:
250864
Hom.:
0
AF XY:
0.000147
AC XY:
20
AN XY:
135632
show subpopulations
Gnomad AFR exome
AF:
0.00278
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000616
AC:
89
AN:
1445004
Hom.:
0
Cov.:
32
AF XY:
0.0000476
AC XY:
34
AN XY:
714672
show subpopulations
Gnomad4 AFR exome
AF:
0.00241
Gnomad4 AMR exome
AF:
0.0000676
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000273
Gnomad4 OTH exome
AF:
0.0000504
GnomAD4 genome
AF:
0.000604
AC:
92
AN:
152240
Hom.:
0
Cov.:
32
AF XY:
0.000618
AC XY:
46
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.00219
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000754
Hom.:
0
Bravo
AF:
0.000657

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Mar 29, 2018
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
-0.63
CADD
Benign
4.7
DANN
Benign
0.91
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00011
dbscSNV1_RF
Benign
0.056
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs114191591; hg19: chr1-109779177; API