12-52241562-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.81

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
KRT7	NM_005556.4	c.784G>A	p.Ala262Thr	missense_variant	5/9	ENST00000331817.6
KRT7	XM_011538325.3	c.784G>A	p.Ala262Thr	missense_variant	5/8
KRT7	XM_047428827.1	c.784G>A	p.Ala262Thr	missense_variant	5/7
KRT7	XM_017019294.2	c.253G>A	p.Ala85Thr	missense_variant	3/7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2651 AN: 152222 Hom.: 91 Cov.: 33

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.: 36 AF XY: 0.00371 AC XY: 503 AN XY: 135620

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.: 84 Cov.: 32 AF XY: 0.00172 AC XY: 1249 AN XY: 727128

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.: 92 Cov.: 33 AF XY: 0.0167 AC XY: 1241 AN XY: 74496

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.: 20

Bravo AF: 0.0192

ESP6500AA AF: 0.0533 AC: 235

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00618 AC: 750

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000296

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.23
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.57	T;T
MetaRNN	Benign	0.0082	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.41	T
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	T
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

Other links and lift over

dbSNP: rs116303953; hg19: chr12-52635346; COSMIC: COSV59330014; COSMIC: COSV59330014;