Variant chr1-152910289-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005547.4(IVL):c.492G>A(p.Lys164Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,609,850 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 20 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 9 hom. )

Consequence

IVL
NM_005547.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.228

Variant links:

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]

IVL links:

ENSG00000289062 (HGNC:):

ENSG00000289062 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-152910289-G-A is Benign according to our data. Variant chr1-152910289-G-A is described in ClinVar as [Benign]. Clinvar id is 720995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.228 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00965 (1468/152182) while in subpopulation AFR AF= 0.0334 (1384/41478). AF 95% confidence interval is 0.0319. There are 20 homozygotes in gnomad4. There are 666 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IVL	NM_005547.4 linkuse as main transcript	c.492G>A	p.Lys164Lys	synonymous_variant	2/2	ENST00000368764.4	NP_005538.2	P07476

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IVL	ENST00000368764.4 linkuse as main transcript	c.492G>A	p.Lys164Lys	synonymous_variant	2/2	2	NM_005547.4	ENSP00000357753.3	P07476
ENSG00000289062	ENST00000686895.2 linkuse as main transcript	n.94+2752C>T		intron_variant
ENSG00000289062	ENST00000702923.1 linkuse as main transcript	n.238+2584C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00960

AC:

1460

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0333

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00109

AC:

268

AN:

245412

Hom.:

AF XY:

0.000784

AC XY:

104

AN XY:

132688

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.000707

Gnomad ASJ exome

AF:

0.000505

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.0000665

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000810

Gnomad OTH exome

AF:

0.000827

GnomAD4 exome

AF:

0.000471

AC:

687

AN:

1457668

Hom.:

Cov.:

AF XY:

0.000401

AC XY:

291

AN XY:

724996

show subpopulations

Gnomad4 AFR exome

AF:

0.0149

Gnomad4 AMR exome

AF:

0.000995

Gnomad4 ASJ exome

AF:

0.000769

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000699

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00965

AC:

1468

AN:

152182

Hom.:

Cov.:

AF XY:

0.00895

AC XY:

666

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0334

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00411

Hom.:

Bravo

AF:

0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 04, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.59

DANN

Benign

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over