Variant 12-52241562-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005556.4(KRT7):c.784G>A(p.Ala262Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00337 in 1,613,968 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 92 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 84 hom. )

Consequence

KRT7
NM_005556.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.81

Variant links:

Genes affected

KRT7 (HGNC:6445): (keratin 7) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

KRT7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008173108).

BP6

Variant 12-52241562-G-A is Benign according to our data. Variant chr12-52241562-G-A is described in ClinVar as [Benign]. Clinvar id is 714178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KRT7	NM_005556.4 linkuse as main transcript	c.784G>A	p.Ala262Thr	missense_variant	5/9	ENST00000331817.6	NP_005547.3
KRT7	XM_011538325.3 linkuse as main transcript	c.784G>A	p.Ala262Thr	missense_variant	5/8		XP_011536627.1
KRT7	XM_047428827.1 linkuse as main transcript	c.784G>A	p.Ala262Thr	missense_variant	5/7		XP_047284783.1
KRT7	XM_017019294.2 linkuse as main transcript	c.253G>A	p.Ala85Thr	missense_variant	3/7		XP_016874783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT7	ENST00000331817.6 linkuse as main transcript	c.784G>A	p.Ala262Thr	missense_variant	5/9	1	NM_005556.4	ENSP00000329243	P1

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

2651

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0607

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00483

AC:

1211

AN:

250970

Hom.:

AF XY:

0.00371

AC XY:

503

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.0621

Gnomad AMR exome

AF:

0.00394

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00189

AC:

2766

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

1249

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0626

Gnomad4 AMR exome

AF:

0.00441

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.00411

GnomAD4 genome

AF:

0.0175

AC:

2666

AN:

152340

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1241

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0609

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00822

Hom.:

Bravo

AF:

0.0192

ESP6500AA

AF:

0.0533

AC:

235

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00618

AC:

750

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0082

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.4

D;.

REVEL

Uncertain

0.55

Sift

Uncertain

0.013

D;.

Sift4G

Benign

0.062

T;.

Polyphen

0.94

P;.

Vest4

0.30

MVP

0.79

MPC

0.95

ClinPred

0.028

GERP RS

4.9

Varity_R

0.37

gMVP

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over