19-10103816-T-C

Position:

• chr19-10103816-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ANGPTL6	NM_001387347.1	c.-99-1160A>G		intron_variant			NP_001374276.1
ANGPTL6	NM_001387348.1	c.-99-1160A>G		intron_variant			NP_001374277.1
ANGPTL6	XM_011528349.4	c.-45-679A>G		intron_variant			XP_011526651.1
		n.10103816T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.308

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6511435; hg19: chr19-10214492;