8-18085340-T-C

Position:

• chr8-18085340-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000499554.6(ASAH1-AS1):​n.171T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0582 in 165,822 control chromosomes in the GnomAD database, including 323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (304 hom., cov: 32)
  • Exomes 𝑓: 0.040 (19 hom.)
• Consequence: ASAH1-AS1 ENST00000499554.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.388

Genes affected

ASAH1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-18085340-T-C is Benign according to our data. Variant chr8-18085340-T-C is described in ClinVar as [Benign]. Clinvar id is 1243813.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASAH1-AS1	NR_125429.1	n.171T>C		non_coding_transcript_exon_variant	2/5
ASAH1-AS1	NR_125430.1	n.72+401T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASAH1-AS1	ENST00000499554.6	n.171T>C		non_coding_transcript_exon_variant	2/5	3
ASAH1-AS1	ENST00000517747.5	n.150T>C		non_coding_transcript_exon_variant	2/4	3
ASAH1-AS1	ENST00000517798.2	n.955T>C		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9084 AN: 152064 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0469

GnomAD4 exome AF: 0.0403 AC: 549 AN: 13638 Hom.: 19 Cov.: 0 AF XY: 0.0414 AC XY: 307 AN XY: 7412

Gnomad4 AFR exome AF: 0.0978

Gnomad4 AMR exome AF: 0.0173

Gnomad4 ASJ exome AF: 0.0208

Gnomad4 EAS exome AF: 0.0434

Gnomad4 SAS exome AF: 0.0421

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.0473

Gnomad4 OTH exome AF: 0.0366

GnomAD4 genome AF: 0.0598 AC: 9099 AN: 152184 Hom.: 304 Cov.: 32 AF XY: 0.0582 AC XY: 4332 AN XY: 74412

Gnomad4 AFR AF: 0.0861

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.0538

Gnomad4 SAS AF: 0.0587

Gnomad4 FIN AF: 0.0448

Gnomad4 NFE AF: 0.0541

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.0501 Hom.: 226

Bravo AF: 0.0586

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13274069; hg19: chr8-17942849;