2-21044910-T-C

Variant names:

• chr2-21044910-T-C
• rs512535
• ENST00000762411.1:n.73-8T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000762411.1(ENSG00000299295):​n.73-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,018 control chromosomes in the GnomAD database, including 17,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (17914 hom., cov: 32)
• Consequence: ENSG00000299295 ENST00000762411.1 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.324
• Publications: 31 publications found

Genes affected

ENSG00000299295 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-21044910-T-C is Benign according to our data. Variant chr2-21044910-T-C is described in CliVar as Benign. Clinvar id is 3250498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 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
ENSG00000299295	ENST00000762411.1	n.73-8T>C		splice_region_variant, intron_variant	Intron 1 of 2
ENSG00000299295	ENST00000762412.1	n.187-8T>C		splice_region_variant, intron_variant	Intron 1 of 1
ENSG00000299295	ENST00000762413.1	n.55-8T>C		splice_region_variant, intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70277 AN: 151900 Hom.: 17914 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.499

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.462 AC: 70271 AN: 152018 Hom.: 17914 Cov.: 32 AF XY: 0.470 AC XY: 34884 AN XY: 74284

African (AFR) AF: 0.237 AC: 9818 AN: 41482

American (AMR) AF: 0.493 AC: 7521 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3466

East Asian (EAS) AF: 0.792 AC: 4074 AN: 5144

South Asian (SAS) AF: 0.698 AC: 3363 AN: 4818

European-Finnish (FIN) AF: 0.578 AC: 6110 AN: 10562

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36074 AN: 67964

Other (OTH) AF: 0.501 AC: 1056 AN: 2108

Alfa AF: 0.509 Hom.: 80475

Bravo AF: 0.442

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial hypercholesterolemia Benign:1

Jun 30, 2022

GENinCode PLC

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.53
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs512535; hg19: chr2-21267782;