rs639219

Positions:

• chr12-52699818-G-A
• chr12-52699818-G-C

Variant summary

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

The NM_175078.3(KRT77):​c.544-1922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 152,272 control chromosomes in the GnomAD database, including 185 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 0.042 (185 hom., cov: 32)
• Consequence: KRT77 NM_175078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140

Genes affected

KRT77 (HGNC:20411): (keratin 77) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes an epithelial keratin that is expressed in the skin and eccrine sweat glands. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT77	NM_175078.3	c.544-1922C>T		intron_variant		ENST00000341809.8	NP_778253.2
KRT77	XM_011538289.3	c.544-1922C>T		intron_variant			XP_011536591.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT77	ENST00000341809.8	c.544-1922C>T		intron_variant		1	NM_175078.3	ENSP00000342710	P1
KRT77	ENST00000553168.1	c.544-1558C>T		intron_variant, NMD_transcript_variant		1		ENSP00000448207

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6437 AN: 152154 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0896

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0410

Gnomad OTH AF: 0.0478

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

GnomAD4 genome AF: 0.0423 AC: 6441 AN: 152272 Hom.: 185 Cov.: 32 AF XY: 0.0457 AC XY: 3404 AN XY: 74432

Gnomad4 AFR AF: 0.0295

Gnomad4 AMR AF: 0.0282

Gnomad4 ASJ AF: 0.0423

Gnomad4 EAS AF: 0.0922

Gnomad4 SAS AF: 0.0644

Gnomad4 FIN AF: 0.0896

Gnomad4 NFE AF: 0.0410

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0191 Hom.: 10

Bravo AF: 0.0362

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.48

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: rs639219; hg19: chr12-53093602;