8-18085242-G-T

Position:

• chr8-18085242-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000499554.6(ASAH1-AS1):​n.73G>T variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 248,932 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: ASAH1-AS1 ENST00000499554.6 splice_region, non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.04

Genes affected

ASAH1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-18085242-G-T is Benign according to our data. Variant chr8-18085242-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1191485.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00554 (840/151522) while in subpopulation AFR AF= 0.0189 (782/41394). AF 95% confidence interval is 0.0178. There are 6 homozygotes in gnomad4. There are 417 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASAH1-AS1	NR_125429.1	n.73G>T		splice_region_variant, non_coding_transcript_exon_variant	2/5
ASAH1-AS1	NR_125430.1	n.72+303G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASAH1-AS1	ENST00000499554.6	n.73G>T		splice_region_variant, non_coding_transcript_exon_variant	2/5	3
ASAH1-AS1	ENST00000517747.5	n.52G>T		splice_region_variant, non_coding_transcript_exon_variant	2/4	3
ASAH1-AS1	ENST00000517798.2	n.857G>T		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes AF: 0.00554 AC: 839 AN: 151420 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

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: 0.0000884

Gnomad OTH AF: 0.00481

GnomAD4 exome AF: 0.000267 AC: 26 AN: 97410 Hom.: 0 Cov.: 0 AF XY: 0.000174 AC XY: 9 AN XY: 51594

Gnomad4 AFR exome AF: 0.00738

Gnomad4 AMR exome AF: 0.00124

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: 0.00

Gnomad4 OTH exome AF: 0.000421

GnomAD4 genome AF: 0.00554 AC: 840 AN: 151522 Hom.: 6 Cov.: 32 AF XY: 0.00564 AC XY: 417 AN XY: 73988

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000884

Gnomad4 OTH AF: 0.00478

Alfa AF: 0.00402 Hom.: 0

Bravo AF: 0.00640

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs181813689; hg19: chr8-17942751;