12-52589497-C-G

Variant names:

• chr12-52589497-C-G
• rs681812
• NM_080747.3:c.1089+1339G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000293745.7(KRT72):​c.1089+1339G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,192 control chromosomes in the GnomAD database, including 49,180 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 0.80 (49180 hom., cov: 33)
• Consequence: KRT72 ENST00000293745.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 2 publications found

Genes affected

KRT72 (HGNC:28932): (keratin 72) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells. The type II keratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This gene encodes a type II keratin that is specifically expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q12-q13. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000293745.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT72	NM_080747.3	MANE Select	c.1089+1339G>C		intron	N/A	NP_542785.1
	KRT72	NM_001146225.2		c.1089+1339G>C		intron	N/A	NP_001139697.1
	KRT72	NM_001146226.2		c.964-1646G>C		intron	N/A	NP_001139698.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT72	ENST00000293745.7	TSL:1 MANE Select	c.1089+1339G>C		intron	N/A	ENSP00000293745.2
	KRT72	ENST00000537672.6	TSL:2	c.1089+1339G>C		intron	N/A	ENSP00000441160.2
	KRT72	ENST00000354310.4	TSL:2	c.964-1646G>C		intron	N/A	ENSP00000346269.4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121189 AN: 152074 Hom.: 49117 Cov.: 33

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.797 AC: 121309 AN: 152192 Hom.: 49180 Cov.: 33 AF XY: 0.791 AC XY: 58827 AN XY: 74396

African (AFR) AF: 0.954 AC: 39638 AN: 41540

American (AMR) AF: 0.696 AC: 10653 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2395 AN: 3470

East Asian (EAS) AF: 0.776 AC: 4023 AN: 5186

South Asian (SAS) AF: 0.774 AC: 3729 AN: 4820

European-Finnish (FIN) AF: 0.724 AC: 7653 AN: 10576

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50641 AN: 67986

Other (OTH) AF: 0.777 AC: 1642 AN: 2114

Alfa AF: 0.775 Hom.: 5743

Bravo AF: 0.801

Asia WGS AF: 0.795 AC: 2763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs681812; hg19: chr12-52983281;