dbSNP rs584436: KRT74:c.*685G>A (chr12-52566284-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.80

Publications

6 publications found

Variant links:

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

KRT74 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KRT74	NM_175053.4 link	c.*685G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000305620.3	NP_778223.2	Q7RTS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT74	ENST00000305620.3 link	c.*685G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_175053.4	ENSP00000307240.2		Q7RTS7
KRT74	ENST00000549343.5 link	c.*685G>A		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000447447.1		F8W1S1

Frequencies

GnomAD3 genomes

AF:

0.729

AC:

110457

AN:

151500

Hom.:

41090

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.550

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.729

AC:

110565

AN:

151618

Hom.:

41142

Cov.:

AF XY:

0.726

AC XY:

53709

AN XY:

74030

show subpopulations

African (AFR)

AF:

0.879

AC:

36339

AN:

41326

American (AMR)

AF:

0.617

AC:

9397

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

2039

AN:

3468

East Asian (EAS)

AF:

0.660

AC:

3379

AN:

5116

South Asian (SAS)

AF:

0.751

AC:

3601

AN:

4796

European-Finnish (FIN)

AF:

0.698

AC:

7324

AN:

10496

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.680

AC:

46156

AN:

67902

Other (OTH)

AF:

0.699

AC:

1462

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1456

2911

4367

5822

7278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.682

Hom.:

45234

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

(source)

DANN

Benign

0.29

PhyloP100

-3.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over