Genetic Variant NM_033448.3:c.1524A>G (chr12-52544580-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033448.3(KRT71):c.1524A>G(p.Leu508Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,613,698 control chromosomes in the GnomAD database, including 194,874 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 13944 hom., cov: 32)

Exomes 𝑓: 0.49 ( 180930 hom. )

Consequence

KRT71
NM_033448.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.178

Publications

20 publications found

Variant links:

Genes affected

KRT71 (HGNC:28927): (keratin 71) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT71 Gene-Disease associations (from GenCC):

isolated familial wooly hair disorder
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypotrichosis 13
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

KRT71 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-52544580-T-C is Benign according to our data. Variant chr12-52544580-T-C is described in ClinVar as Benign. ClinVar VariationId is 1257730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.178 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033448.3. 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
	KRT71	NM_033448.3	MANE Select	c.1524A>G	p.Leu508Leu	synonymous	Exon 9 of 9	NP_258259.1	Q3SY84

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT71	ENST00000267119.6	TSL:1 MANE Select	c.1524A>G	p.Leu508Leu	synonymous	Exon 9 of 9	ENSP00000267119.5	Q3SY84

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58453

AN:

151884

Hom.:

13951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0935

Gnomad AMI

AF:

0.529

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.421

GnomAD2 exomes

AF:

0.457

AC:

114963

AN:

251416

AF XY:

0.457

show subpopulations

Gnomad AFR exome

AF:

0.0825

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.510

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.510

Gnomad OTH exome

AF:

0.497

GnomAD4 exome

AF:

0.490

AC:

715709

AN:

1461698

Hom.:

180930

Cov.:

AF XY:

0.486

AC XY:

353061

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.0788

AC:

2639

AN:

33478

American (AMR)

AF:

0.516

AC:

23082

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.579

AC:

15134

AN:

26134

East Asian (EAS)

AF:

0.534

AC:

21185

AN:

39698

South Asian (SAS)

AF:

0.308

AC:

26555

AN:

86256

European-Finnish (FIN)

AF:

0.462

AC:

24657

AN:

53356

Middle Eastern (MID)

AF:

0.548

AC:

3160

AN:

5766

European-Non Finnish (NFE)

AF:

0.513

AC:

570620

AN:

1111902

Other (OTH)

AF:

0.475

AC:

28677

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

20695

41390

62085

82780

103475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16268

32536

48804

65072

81340

<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:

0.384

AC:

58433

AN:

152000

Hom.:

13944

Cov.:

AF XY:

0.384

AC XY:

28493

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0933

AC:

3870

AN:

41498

American (AMR)

AF:

0.471

AC:

7204

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.595

AC:

2062

AN:

3464

East Asian (EAS)

AF:

0.525

AC:

2705

AN:

5156

South Asian (SAS)

AF:

0.298

AC:

1434

AN:

4812

European-Finnish (FIN)

AF:

0.450

AC:

4758

AN:

10572

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.514

AC:

34880

AN:

67902

Other (OTH)

AF:

0.417

AC:

879

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1610

3220

4831

6441

8051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.484

Hom.:

45203

Bravo

AF:

0.378

Asia WGS

AF:

0.357

AC:

1241

AN:

3478

EpiCase

AF:

0.530

EpiControl

AF:

0.525

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.7

(source)

DANN

Benign

0.74

PhyloP100

0.18

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over