rs8112063

Positions:

• chr19-10099035-C-T

Variant summary

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

The ENST00000253109.5(ANGPTL6):​c.-10-2462G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,802 control chromosomes in the GnomAD database, including 20,247 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 0.51 (20247 hom., cov: 30)
• Consequence: ANGPTL6 ENST00000253109.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPTL6	NM_031917.3	c.-10-2462G>A		intron_variant		ENST00000253109.5	NP_114123.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPTL6	ENST00000253109.5	c.-10-2462G>A		intron_variant		1	NM_031917.3	ENSP00000253109	P1
ANGPTL6	ENST00000592641.5	c.-10-2462G>A		intron_variant		1		ENSP00000467930	P1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77571 AN: 151684 Hom.: 20259 Cov.: 30

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.511 AC: 77558 AN: 151802 Hom.: 20247 Cov.: 30 AF XY: 0.505 AC XY: 37488 AN XY: 74180

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.530

Alfa AF: 0.541 Hom.: 18221

Bravo AF: 0.504

Asia WGS AF: 0.405 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.7
DANN	Benign	0.80

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: rs8112063; hg19: chr19-10209711;