rs7517189

Positions:

• chr1-152909270-C-G
• chr1-152909270-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005547.4(IVL):​c.-19-509C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,046 control chromosomes in the GnomAD database, including 9,309 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 0.27 (9309 hom., cov: 32)
• Consequence: IVL NM_005547.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IVL	NM_005547.4	c.-19-509C>G		intron_variant		ENST00000368764.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IVL	ENST00000368764.4	c.-19-509C>G		intron_variant		2	NM_005547.4	P1
	ENST00000686895.2	n.94+3771G>C		intron_variant, non_coding_transcript_variant
	ENST00000702923.1	n.238+3603G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40611 AN: 151928 Hom.: 9269 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.0902

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.210

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.268 AC: 40699 AN: 152046 Hom.: 9309 Cov.: 32 AF XY: 0.269 AC XY: 19997 AN XY: 74336

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.0902

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0938

Gnomad4 OTH AF: 0.211

Alfa AF: 0.185 Hom.: 676

Bravo AF: 0.300

Asia WGS AF: 0.398 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.19
DANN	Benign	0.42

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: rs7517189; hg19: chr1-152881746;