NM_031917.3:c.-10-1943C>G

Variant names:

• chr19-10098516-G-C
• rs11671983
• NM_031917.3:c.-10-1943C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031917.3(ANGPTL6):​c.-10-1943C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,098 control chromosomes in the GnomAD database, including 1,123 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 0.12 (1123 hom., cov: 31)
• Consequence: ANGPTL6 NM_031917.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 3 publications found

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]

ANGPTL6 Gene-Disease associations (from GenCC):

• intracranial berry aneurysm

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPTL6	NM_031917.3	c.-10-1943C>G		intron_variant	Intron 1 of 5	ENST00000253109.5	NP_114123.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPTL6	ENST00000253109.5	c.-10-1943C>G		intron_variant	Intron 1 of 5	1	NM_031917.3	ENSP00000253109.3
ANGPTL6	ENST00000592641.5	c.-10-1943C>G		intron_variant	Intron 1 of 5	1		ENSP00000467930.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17613 AN: 151978 Hom.: 1122 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.116 AC: 17611 AN: 152098 Hom.: 1123 Cov.: 31 AF XY: 0.115 AC XY: 8535 AN XY: 74356

African (AFR) AF: 0.101 AC: 4179 AN: 41482

American (AMR) AF: 0.106 AC: 1623 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3464

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5174

South Asian (SAS) AF: 0.0732 AC: 353 AN: 4820

European-Finnish (FIN) AF: 0.165 AC: 1750 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8782 AN: 67972

Other (OTH) AF: 0.135 AC: 285 AN: 2112

Alfa AF: 0.122 Hom.: 136

Bravo AF: 0.114

Asia WGS AF: 0.0420 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11671983; hg19: chr19-10209192;