14-76818376-T-C

Position:

• chr14-76818376-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000557497.1(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 ENST00000557497.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.76818376T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGEL1	ENST00000557497.1	c.-12-3955A>G		intron_variant		2		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

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.409

Alfa AF: 0.381 Hom.: 9560

Bravo AF: 0.401

Asia WGS AF: 0.552 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs760267; hg19: chr14-77284719;