rs10863899

Variant names:

• chr1-211492876-A-G
• rs10863899
• ENST00000417794.1:n.450A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

Genes affected

ENSG00000223649 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000223649	ENST00000417794.1	n.450A>G		non_coding_transcript_exon_variant	Exon 2 of 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

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.262 AC: 11 AN: 42

Other (OTH) AF: 0.500 AC: 3 AN: 6

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

African (AFR) AF: 0.624 AC: 25880 AN: 41474

American (AMR) AF: 0.374 AC: 5711 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1556 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2186 AN: 5160

South Asian (SAS) AF: 0.398 AC: 1918 AN: 4816

European-Finnish (FIN) AF: 0.325 AC: 3446 AN: 10590

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28773 AN: 67958

Other (OTH) AF: 0.461 AC: 972 AN: 2108

Alfa AF: 0.438 Hom.: 47776

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

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.62
PhyloP100		-0.46
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10863899; hg19: chr1-211666218;