NM_031917.3:c.-11+90C>T

Variant names:

• chr19-10102478-G-A
• rs8109578
• NM_031917.3:c.-11+90C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031917.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL6	NM_031917.3	MANE Select	c.-11+90C>T		intron	N/A	NP_114123.2
	ANGPTL6	NM_001321411.2		c.-11+74C>T		intron	N/A	NP_001308340.1
	ANGPTL6	NM_001387347.1		c.-11+90C>T		intron	N/A	NP_001374276.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL6	ENST00000253109.5	TSL:1 MANE Select	c.-11+90C>T		intron	N/A	ENSP00000253109.3
	ANGPTL6	ENST00000592641.5	TSL:1	c.-11+74C>T		intron	N/A	ENSP00000467930.1

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

African (AFR) AF: 0.0550 AC: 697 AN: 12672

American (AMR) AF: 0.0510 AC: 39 AN: 764

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 298 AN: 4274

East Asian (EAS) AF: 0.000337 AC: 1 AN: 2968

South Asian (SAS) AF: 0.0480 AC: 647 AN: 13490

European-Finnish (FIN) AF: 0.0955 AC: 21 AN: 220

Middle Eastern (MID) AF: 0.0659 AC: 89 AN: 1350

European-Non Finnish (NFE) AF: 0.103 AC: 63010 AN: 610640

Other (OTH) AF: 0.0873 AC: 1926 AN: 22068

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

African (AFR) AF: 0.0565 AC: 2344 AN: 41460

American (AMR) AF: 0.0581 AC: 885 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0580 AC: 201 AN: 3468

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5156

South Asian (SAS) AF: 0.0419 AC: 202 AN: 4824

European-Finnish (FIN) AF: 0.0860 AC: 897 AN: 10430

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7181 AN: 67648

Other (OTH) AF: 0.0635 AC: 133 AN: 2096

Alfa AF: 0.0893 Hom.: 1546

Bravo AF: 0.0745

Asia WGS AF: 0.0210 AC: 74 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		0.085
PromoterAI		0.067	Neutral
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: rs8109578; hg19: chr19-10213154;