12-52567370-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_175053.4(KRT74):c.1391-202T>C 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 151,536 control chromosomes in the GnomAD database, including 43,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.75 (43468 hom., cov: 31)
• Consequence: KRT74 NM_175053.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0200

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-52567370-A-G is Benign according to our data. Variant chr12-52567370-A-G is described in ClinVar as [Benign]. Clinvar id is 1265618.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
KRT74	NM_175053.4	c.1391-202T>C		intron_variant		ENST00000305620.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT74	ENST00000305620.3	c.1391-202T>C		intron_variant		1	NM_175053.4	P1
KRT74	ENST00000549343.5	c.1433-202T>C		intron_variant		5
KRT74	ENST00000546384.1	n.378-202T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.746 AC: 112966 AN: 151420 Hom.: 43404 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: 0.658

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: 113085 AN: 151536 Hom.: 43468 Cov.: 31 AF XY: 0.742 AC XY: 54919 AN XY: 74022

Gnomad4 AFR AF: 0.941

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.707

Alfa AF: 0.726 Hom.: 4986

Bravo AF: 0.746

Asia WGS AF: 0.755 AC: 2627 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.93
Cadd	Benign	3.7
Dann	Benign	0.43

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: rs611756; hg19: chr12-52961154;