rs584436

Positions:

• chr12-52566284-C-T

Variant summary

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

The NM_175053.4(KRT74):​c.*685G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 151,652 control chromosomes in the GnomAD database, including 41,150 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 0.73 (41142 hom., cov: 29)
  • Exomes 𝑓: 0.68 (8 hom.)
• Consequence: KRT74 NM_175053.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.80

Genes affected

KRT74 (HGNC:28929): (keratin 74) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This protein belongs to a family of keratins that are specifically expressed in the inner root sheath of hair follicles.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT74	NM_175053.4	c.*685G>A		3_prime_UTR_variant	9/9	ENST00000305620.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT74	ENST00000305620.3	c.*685G>A		3_prime_UTR_variant	9/9	1	NM_175053.4	P1
KRT74	ENST00000549343.5	c.*685G>A		3_prime_UTR_variant	10/10	5

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110457 AN: 151500 Hom.: 41090 Cov.: 29

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.698

GnomAD4 exome AF: 0.676 AC: 23 AN: 34 Hom.: 8 Cov.: 0 AF XY: 0.667 AC XY: 12 AN XY: 18

Gnomad4 AMR exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.550

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.729 AC: 110565 AN: 151618 Hom.: 41142 Cov.: 29 AF XY: 0.726 AC XY: 53709 AN XY: 74030

Gnomad4 AFR AF: 0.879

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.699

Alfa AF: 0.673 Hom.: 33703

Bravo AF: 0.725

Asia WGS AF: 0.750 AC: 2611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.028
DANN	Benign	0.29

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: rs584436; hg19: chr12-52960068;