14-76818376-T-C

Variant names:

• chr14-76818376-T-C
• rs760267
• ENST00000557497.2:c.-12-3955A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000557497.2(ANGEL1):​c.-12-3955A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,004 control chromosomes in the GnomAD database, including 12,541 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12541 hom., cov: 32)
• Consequence: ANGEL1 ENST00000557497.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802
• Publications: 3 publications found

Genes affected

ANGEL1 (HGNC:19961): (angel homolog 1) Enables eukaryotic initiation factor 4E binding activity and protein domain specific binding activity. Predicted to be involved in RNA phosphodiester bond hydrolysis, exonucleolytic. Located in several cellular components, including cis-Golgi network; endoplasmic reticulum; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000557497.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGEL1	ENST00000557497.2	TSL:2	c.-12-3955A>G		intron	N/A	ENSP00000498076.2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60939 AN: 151886 Hom.: 12534 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.401 AC: 60982 AN: 152004 Hom.: 12541 Cov.: 32 AF XY: 0.406 AC XY: 30160 AN XY: 74282

African (AFR) AF: 0.371 AC: 15402 AN: 41466

American (AMR) AF: 0.399 AC: 6101 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1557 AN: 3468

East Asian (EAS) AF: 0.653 AC: 3370 AN: 5160

South Asian (SAS) AF: 0.531 AC: 2556 AN: 4818

European-Finnish (FIN) AF: 0.374 AC: 3943 AN: 10546

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26667 AN: 67962

Other (OTH) AF: 0.409 AC: 863 AN: 2112

Alfa AF: 0.383 Hom.: 11425

Bravo AF: 0.401

Asia WGS AF: 0.552 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.87
DANN	Benign	0.81
PhyloP100		-0.80

Splicing

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

Other links and lift over

dbSNP: rs760267; hg19: chr14-77284719;