rs592720

Variant names:

• chr12-52574076-A-G
• rs592720
• NM_175053.4:c.-299T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-52574076-A-G
• chr12-52574076-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_175053.4(KRT74):​c.-299T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,166 control chromosomes in the GnomAD database, including 48,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.79 (48886 hom., cov: 32)
• Consequence: KRT74 NM_175053.4 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.679
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant wooly hair

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hypotrichosis 3

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• hypotrichosis simplex of the scalp

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated familial wooly hair disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pure hair and nail ectodermal dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 12-52574076-A-G is Benign according to our data. Variant chr12-52574076-A-G is described in ClinVar as Benign. ClinVar VariationId is 1225607.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175053.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT74	NM_175053.4	MANE Select	c.-299T>C		upstream_gene	N/A	NP_778223.2	Q7RTS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT74	ENST00000305620.3	TSL:1 MANE Select	c.-299T>C		upstream_gene	N/A	ENSP00000307240.2	Q7RTS7

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120744 AN: 152048 Hom.: 48823 Cov.: 32

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.794 AC: 120864 AN: 152166 Hom.: 48886 Cov.: 32 AF XY: 0.789 AC XY: 58679 AN XY: 74366

African (AFR) AF: 0.953 AC: 39593 AN: 41542

American (AMR) AF: 0.679 AC: 10378 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2354 AN: 3470

East Asian (EAS) AF: 0.708 AC: 3647 AN: 5152

South Asian (SAS) AF: 0.787 AC: 3791 AN: 4818

European-Finnish (FIN) AF: 0.747 AC: 7902 AN: 10584

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50628 AN: 67986

Other (OTH) AF: 0.772 AC: 1632 AN: 2114

Alfa AF: 0.781 Hom.: 6773

Bravo AF: 0.794

Asia WGS AF: 0.771 AC: 2679 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		0.68
PromoterAI		0.0039	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs592720; hg19: chr12-52967860;