12-52567433-C-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.1390+226G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 152,180 control chromosomes in the GnomAD database, including 613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.062 (613 hom., cov: 32)
• Consequence: KRT74 NM_175053.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.716

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=-0.84).
• BP6: Variant 12-52567433-C-G is Benign according to our data. Variant chr12-52567433-C-G is described in ClinVar as [Benign]. Clinvar id is 1242399.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT74	NM_175053.4	c.1390+226G>C		intron_variant		ENST00000305620.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT74	ENST00000305620.3	c.1390+226G>C		intron_variant		1	NM_175053.4	P1
KRT74	ENST00000549343.5	c.1432+226G>C		intron_variant		5
KRT74	ENST00000546384.1	n.377+226G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9374 AN: 152062 Hom.: 605 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0805

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00206

Gnomad OTH AF: 0.0527

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

GnomAD4 genome AF: 0.0618 AC: 9404 AN: 152180 Hom.: 613 Cov.: 32 AF XY: 0.0650 AC XY: 4836 AN XY: 74396

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0804

Gnomad4 FIN AF: 0.0464

Gnomad4 NFE AF: 0.00206

Gnomad4 OTH AF: 0.0522

Alfa AF: 0.0332 Hom.: 35

Bravo AF: 0.0718

Asia WGS AF: 0.133 AC: 463 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.4
Dann	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3858633; hg19: chr12-52961217;