19-10092495-A-G

Position:

• chr19-10092495-A-G

Variant summary

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

The NM_031917.3(ANGPTL6):​c.*94T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 1,523,504 control chromosomes in the GnomAD database, including 6,462 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 0.072 (476 hom., cov: 32)
  • Exomes 𝑓: 0.089 (5986 hom.)
• Consequence: ANGPTL6 NM_031917.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397

Genes affected

ANGPTL6 (HGNC:23140): (angiopoietin like 6) Predicted to enable signaling receptor binding activity. Predicted to be involved in angiogenesis and cell differentiation. Located in extracellular exosome. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

SHFL (HGNC:25649): (shiftless antiviral inhibitor of ribosomal frameshifting) This gene is an interferon stimulated gene (ISG) that inhibits viral replication. The encoded protein binds nucleic acids and inhibits programmed -1 ribosomal frameshifting required for translation by many RNA viruses. Viruses inhibited by the protein include Zika virus, dengue virus and the coronaviruses, SARS-CoV and SARS-CoV2. [provided by RefSeq, Aug 2021]

SHFL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPTL6	NM_031917.3	c.*94T>C		3_prime_UTR_variant	6/6	ENST00000253109.5	NP_114123.2
SHFL	NM_018381.4	c.*193A>G		3_prime_UTR_variant	8/8	ENST00000253110.16	NP_060851.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPTL6	ENST00000253109	c.*94T>C		3_prime_UTR_variant	6/6	1	NM_031917.3	ENSP00000253109.3
SHFL	ENST00000253110.16	c.*193A>G		3_prime_UTR_variant	8/8	2	NM_018381.4	ENSP00000253110.10

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10979 AN: 152122 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0583

GnomAD4 exome AF: 0.0891 AC: 122122 AN: 1371264 Hom.: 5986 Cov.: 27 AF XY: 0.0878 AC XY: 59312 AN XY: 675456

Gnomad4 AFR exome AF: 0.0366

Gnomad4 AMR exome AF: 0.0394

Gnomad4 ASJ exome AF: 0.0697

Gnomad4 EAS exome AF: 0.000308

Gnomad4 SAS exome AF: 0.0481

Gnomad4 FIN exome AF: 0.0825

Gnomad4 NFE exome AF: 0.0997

Gnomad4 OTH exome AF: 0.0771

GnomAD4 genome AF: 0.0722 AC: 10986 AN: 152240 Hom.: 476 Cov.: 32 AF XY: 0.0703 AC XY: 5233 AN XY: 74418

Gnomad4 AFR AF: 0.0373

Gnomad4 AMR AF: 0.0564

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0441

Gnomad4 FIN AF: 0.0844

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0907 Hom.: 1180

Bravo AF: 0.0670

Asia WGS AF: 0.0220 AC: 76 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.63
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs15723; hg19: chr19-10203171;