11-101891348-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_178127.5(ANGPTL5):c.1097_1098insA(p.Asn366LysfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000711 in 1,613,972 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00084 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (15 hom.)
• Consequence: ANGPTL5 NM_178127.5 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.08

Genes affected

ANGPTL5 (HGNC:19705): (angiopoietin like 5) Predicted to be active in collagen-containing extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-101891348-G-GT is Benign according to our data. Variant chr11-101891348-G-GT is described in ClinVar as [Benign]. Clinvar id is 715516.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000841 (128/152216) while in subpopulation EAS AF= 0.0224 (116/5188). AF 95% confidence interval is 0.0191. There are 1 homozygotes in gnomad4. There are 79 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPTL5	NM_178127.5	c.1097_1098insA	p.Asn366LysfsTer8	frameshift_variant	9/9	ENST00000334289.7
ANGPTL5	XM_011542735.4	c.902_903insA	p.Asn301LysfsTer8	frameshift_variant	7/7
ANGPTL5	XM_017017466.3	c.677_678insA	p.Asn226LysfsTer8	frameshift_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGPTL5	ENST00000334289.7	c.1097_1098insA	p.Asn366LysfsTer8	frameshift_variant	9/9	1	NM_178127.5	P1

Frequencies

GnomAD3 genomes AF: 0.000842 AC: 128 AN: 152098 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00205 AC: 516 AN: 251236 Hom.: 6 AF XY: 0.00191 AC XY: 259 AN XY: 135786

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0261

Gnomad SAS exome AF: 0.000719

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000698 AC: 1020 AN: 1461756 Hom.: 15 Cov.: 31 AF XY: 0.000722 AC XY: 525 AN XY: 727184

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0209

Gnomad4 SAS exome AF: 0.000684

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.00171

GnomAD4 genome AF: 0.000841 AC: 128 AN: 152216 Hom.: 1 Cov.: 32 AF XY: 0.00106 AC XY: 79 AN XY: 74418

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.00120

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs199645342; hg19: chr11-101762079;