19-10102478-G-A

Position:

• chr19-10102478-G-A

Variant summary

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

The NM_031917.3(ANGPTL6):​c.-11+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 819,958 control chromosomes in the GnomAD database, including 4,523 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 0.079 (683 hom., cov: 31)
  • Exomes 𝑓: 0.10 (3840 hom.)
• Consequence: ANGPTL6 NM_031917.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPTL6	NM_031917.3	c.-11+90C>T		intron_variant		ENST00000253109.5	NP_114123.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPTL6	ENST00000253109.5	c.-11+90C>T		intron_variant		1	NM_031917.3	ENSP00000253109	P1
ANGPTL6	ENST00000592641.5	c.-11+74C>T		intron_variant		1		ENSP00000467930	P1

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 11953 AN: 151394 Hom.: 683 Cov.: 31

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0580

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.0860

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0641

GnomAD4 exome AF: 0.0998 AC: 66728 AN: 668446 Hom.: 3840 AF XY: 0.0991 AC XY: 30842 AN XY: 311164

Gnomad4 AFR exome AF: 0.0550

Gnomad4 AMR exome AF: 0.0510

Gnomad4 ASJ exome AF: 0.0697

Gnomad4 EAS exome AF: 0.000337

Gnomad4 SAS exome AF: 0.0480

Gnomad4 FIN exome AF: 0.0955

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.0873

GnomAD4 genome AF: 0.0789 AC: 11958 AN: 151512 Hom.: 683 Cov.: 31 AF XY: 0.0764 AC XY: 5651 AN XY: 74006

Gnomad4 AFR AF: 0.0565

Gnomad4 AMR AF: 0.0581

Gnomad4 ASJ AF: 0.0580

Gnomad4 EAS AF: 0.000970

Gnomad4 SAS AF: 0.0419

Gnomad4 FIN AF: 0.0860

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0635

Alfa AF: 0.0921 Hom.: 933

Bravo AF: 0.0745

Asia WGS AF: 0.0210 AC: 74 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.64

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: rs8109578; hg19: chr19-10213154;