19-10103816-T-C

Variant names:

• chr19-10103816-T-C
• rs6511435
• NM_001387347.1:c.-99-1160A>G

Variant summary

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

The NM_001387347.1(ANGPTL6):​c.-99-1160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 150,948 control chromosomes in the GnomAD database, including 8,035 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 0.31 (8035 hom., cov: 32)
• Consequence: ANGPTL6 NM_001387347.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPTL6	NM_001387347.1	c.-99-1160A>G		intron_variant	Intron 1 of 6		NP_001374276.1
ANGPTL6	NM_001387348.1	c.-99-1160A>G		intron_variant	Intron 1 of 6		NP_001374277.1
ANGPTL6	XM_011528349.4	c.-45-679A>G		intron_variant	Intron 1 of 7		XP_011526651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46077 AN: 150830 Hom.: 8024 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.305 AC: 46108 AN: 150948 Hom.: 8035 Cov.: 32 AF XY: 0.298 AC XY: 21973 AN XY: 73718

African (AFR) AF: 0.436 AC: 18025 AN: 41362

American (AMR) AF: 0.245 AC: 3720 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3462

East Asian (EAS) AF: 0.154 AC: 796 AN: 5170

South Asian (SAS) AF: 0.182 AC: 878 AN: 4818

European-Finnish (FIN) AF: 0.194 AC: 1946 AN: 10036

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18768 AN: 67620

Other (OTH) AF: 0.308 AC: 645 AN: 2092

Alfa AF: 0.115 Hom.: 206

Bravo AF: 0.320

Asia WGS AF: 0.178 AC: 619 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.12
PhyloP100		-2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6511435; hg19: chr19-10214492;