rs1076584

Positions:

• chr14-76787756-G-A

Variant summary

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

The NM_015305.4(ANGEL1):​c.*1472C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,518 control chromosomes in the GnomAD database, including 983 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 0.11 (982 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: ANGEL1 NM_015305.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGEL1	NM_015305.4	c.*1472C>T		3_prime_UTR_variant	10/10	ENST00000251089.8
ANGEL1	NM_001370747.1	c.*1472C>T		3_prime_UTR_variant	12/12
ANGEL1	NM_001370746.1	c.2012-1164C>T		intron_variant
ANGEL1	NM_001370748.1	c.1853-1164C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGEL1	ENST00000251089.8	c.*1472C>T		3_prime_UTR_variant	10/10	1	NM_015305.4	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16268 AN: 152086 Hom.: 984 Cov.: 32

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0704

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0938

GnomAD4 exome AF: 0.124 AC: 39 AN: 314 Hom.: 1 Cov.: 0 AF XY: 0.117 AC XY: 23 AN XY: 196

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.0250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.107 AC: 16280 AN: 152204 Hom.: 982 Cov.: 32 AF XY: 0.111 AC XY: 8268 AN XY: 74422

Gnomad4 AFR AF: 0.0945

Gnomad4 AMR AF: 0.0702

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.0869 Hom.: 391

Bravo AF: 0.101

Asia WGS AF: 0.157 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.72
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1076584; hg19: chr14-77254099;