chr1-152910310-A-G

Position:

• chr1-152910310-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_005547.4(IVL):​c.513A>G​(p.Gly171Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: IVL NM_005547.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.07

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-152910310-A-G is Benign according to our data. Variant chr1-152910310-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639342.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IVL	NM_005547.4	c.513A>G	p.Gly171Gly	synonymous_variant	2/2	ENST00000368764.4	NP_005538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IVL	ENST00000368764.4	c.513A>G	p.Gly171Gly	synonymous_variant	2/2	2	NM_005547.4	ENSP00000357753.3
ENSG00000289062	ENST00000686895.2	n.94+2731T>C		intron_variant
ENSG00000289062	ENST00000702923.1	n.238+2563T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 66 AN: 124028 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000528

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000155

Gnomad ASJ AF: 0.000342

Gnomad EAS AF: 0.00152

Gnomad SAS AF: 0.000274

Gnomad FIN AF: 0.000226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000597

Gnomad OTH AF: 0.00178

GnomAD3 exomes AF: 0.0000537 AC: 12 AN: 223450 Hom.: 0 AF XY: 0.0000581 AC XY: 7 AN XY: 120438

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000662

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000994

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000178 AC: 25 AN: 1400892 Hom.: 3 Cov.: 32 AF XY: 0.0000201 AC XY: 14 AN XY: 696340

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000121

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000121

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.0000160

Gnomad4 OTH exome AF: 0.0000347

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000532 AC: 66 AN: 124142 Hom.: 0 Cov.: 31 AF XY: 0.000439 AC XY: 27 AN XY: 61476

Gnomad4 AFR AF: 0.000526

Gnomad4 AMR AF: 0.000155

Gnomad4 ASJ AF: 0.000342

Gnomad4 EAS AF: 0.00152

Gnomad4 SAS AF: 0.000274

Gnomad4 FIN AF: 0.000226

Gnomad4 NFE AF: 0.000597

Gnomad4 OTH AF: 0.00176

Alfa AF: 0.0145 Hom.: 8

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

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

IVL: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.48
DANN	Benign	0.35

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: rs11205135; hg19: chr1-152882786;