1-152910295-AGAGCAGCAGGAGGGACAGCTGAAGCACCCG-A

Position:

• chr1-152910295-AGAGCAGCAGGAGGGACAGCTGAAGCACCCG-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_005547.4(IVL):​c.513_542delACAGCTGAAGCACCCGGAGCAGCAGGAGGG​(p.Gln172_Gly181del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00602 in 148,724 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G171G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0060 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (22 hom.)
  • Failed GnomAD Quality Control
• Consequence: IVL NM_005547.4 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.134

Genes affected

IVL (HGNC:6187): (involucrin) Involucrin, a component of the keratinocyte crosslinked envelope, is found in the cytoplasm and crosslinked to membrane proteins by transglutaminase. This gene is mapped to 1q21, among calpactin I light chain, trichohyalin, profillaggrin, loricrin, and calcyclin. [provided by RefSeq, Jul 2008]

ENSG00000289062 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005547.4.
• BP6: Variant 1-152910295-AGAGCAGCAGGAGGGACAGCTGAAGCACCCG-A is Benign according to our data. Variant chr1-152910295-AGAGCAGCAGGAGGGACAGCTGAAGCACCCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 773814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IVL	NM_005547.4	c.513_542delACAGCTGAAGCACCCGGAGCAGCAGGAGGG	p.Gln172_Gly181del	disruptive_inframe_deletion	2/2	ENST00000368764.4	NP_005538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IVL	ENST00000368764.4	c.513_542delACAGCTGAAGCACCCGGAGCAGCAGGAGGG	p.Gln172_Gly181del	disruptive_inframe_deletion	2/2	2	NM_005547.4	ENSP00000357753.3
ENSG00000289062	ENST00000686895.2	n.94+2716_94+2745delCGGGTGCTTCAGCTGTCCCTCCTGCTGCTC		intron_variant
ENSG00000289062	ENST00000702923.1	n.238+2548_238+2577delCGGGTGCTTCAGCTGTCCCTCCTGCTGCTC		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00605 AC: 899 AN: 148592 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00737

Gnomad ASJ AF: 0.00614

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00515

Gnomad FIN AF: 0.00297

Gnomad MID AF: 0.0166

Gnomad NFE AF: 0.00915

Gnomad OTH AF: 0.0108

GnomAD3 exomes AF: 0.00205 AC: 502 AN: 244422 Hom.: 5 AF XY: 0.00179 AC XY: 236 AN XY: 132024

Gnomad AFR exome AF: 0.000658

Gnomad AMR exome AF: 0.00186

Gnomad ASJ exome AF: 0.00152

Gnomad EAS exome AF: 0.0000553

Gnomad SAS exome AF: 0.000669

Gnomad FIN exome AF: 0.00136

Gnomad NFE exome AF: 0.00310

Gnomad OTH exome AF: 0.00364

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00177 AC: 2572 AN: 1452870 Hom.: 22 AF XY: 0.00197 AC XY: 1421 AN XY: 722186

Gnomad4 AFR exome AF: 0.000450

Gnomad4 AMR exome AF: 0.00188

Gnomad4 ASJ exome AF: 0.00310

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00214

Gnomad4 FIN exome AF: 0.00204

Gnomad4 NFE exome AF: 0.00171

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.00602 AC: 895 AN: 148724 Hom.: 8 Cov.: 32 AF XY: 0.00558 AC XY: 406 AN XY: 72750

Gnomad4 AFR AF: 0.00192

Gnomad4 AMR AF: 0.00736

Gnomad4 ASJ AF: 0.00614

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00494

Gnomad4 FIN AF: 0.00297

Gnomad4 NFE AF: 0.00914

Gnomad4 OTH AF: 0.0107

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs772656711; hg19: chr1-152882771;