rs10863899

Positions:

• chr1-211492876-A-G

Variant summary

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

The ENST00000417794.1(ENSG00000223649):​n.450A>G 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 0.467 in 152,118 control chromosomes in the GnomAD database, including 17,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17484 hom., cov: 33)
  • Exomes 𝑓: 0.36 (6 hom.)
• Consequence: ENSG00000223649 ENST00000417794.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.463

Genes affected

ENSG00000223649 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-211492876-A-G is Benign according to our data. Variant chr1-211492876-A-G is described in ClinVar as [Benign]. Clinvar id is 295305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000223649	ENST00000417794.1	n.450A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70871 AN: 151944 Hom.: 17461 Cov.: 33

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.357 AC: 20 AN: 56 Hom.: 6 Cov.: 0 AF XY: 0.438 AC XY: 14 AN XY: 32

Gnomad4 AFR exome AF: 0.750

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.467 AC: 70953 AN: 152062 Hom.: 17484 Cov.: 33 AF XY: 0.457 AC XY: 34010 AN XY: 74356

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.461

Alfa AF: 0.428 Hom.: 28842

Bravo AF: 0.475

Asia WGS AF: 0.452 AC: 1575 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leber congenital amaurosis 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs10863899; hg19: chr1-211666218;