12-52567369-C-A

Position:

• chr12-52567369-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_175053.4(KRT74):​c.1391-201G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,502 control chromosomes in the GnomAD database, including 43,462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.75 (43462 hom., cov: 31)
• Consequence: KRT74 NM_175053.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17

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]

KRT74 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-52567369-C-A is Benign according to our data. Variant chr12-52567369-C-A is described in ClinVar as [Benign]. Clinvar id is 1243772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT74	NM_175053.4	c.1391-201G>T		intron_variant		ENST00000305620.3	NP_778223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT74	ENST00000305620.3	c.1391-201G>T		intron_variant		1	NM_175053.4	ENSP00000307240.2
KRT74	ENST00000549343.5	c.1433-201G>T		intron_variant		5		ENSP00000447447.1
KRT74	ENST00000546384.1	n.378-201G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.746 AC: 112957 AN: 151386 Hom.: 43398 Cov.: 31

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.651

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.746 AC: 113076 AN: 151502 Hom.: 43462 Cov.: 31 AF XY: 0.742 AC XY: 54909 AN XY: 73998

Gnomad4 AFR AF: 0.941

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.707

Alfa AF: 0.731 Hom.: 5239

Bravo AF: 0.745

Asia WGS AF: 0.755 AC: 2627 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.089
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: rs653956; hg19: chr12-52961153;