Variant 12-52544751-A-G 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_033448.3(KRT71):c.1361-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,600,808 control chromosomes in the GnomAD database, including 195,762 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 14215 hom., cov: 32)

Exomes 𝑓: 0.49 ( 181547 hom. )

Consequence

KRT71
NM_033448.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006541

Clinical Significance

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

Conservation

PhyloP100: 0.242

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 12-52544751-A-G is Benign according to our data. Variant chr12-52544751-A-G is described in ClinVar as [Benign]. Clinvar id is 1237188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KRT71	NM_033448.3 linkuse as main transcript	c.1361-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000267119.6	NP_258259.1
KRT71	XM_017018749.2 linkuse as main transcript	c.1115-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_016874238.1
KRT71	XM_047428196.1 linkuse as main transcript	c.1030-402T>C	intron_variant		XP_047284152.1
KRT71	XM_047428197.1 linkuse as main transcript	c.1235-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_047284153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT71	ENST00000267119.6 linkuse as main transcript	c.1361-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_033448.3	ENSP00000267119	P1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59568

AN:

151970

Hom.:

14223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.544

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.515

Gnomad OTH

AF:

0.429

GnomAD3 exomes

AF:

0.466

AC:

107979

AN:

231654

Hom.:

26529

AF XY:

0.466

AC XY:

58697

AN XY:

125974

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.536

Gnomad SAS exome

AF:

0.349

Gnomad FIN exome

AF:

0.455

Gnomad NFE exome

AF:

0.510

Gnomad OTH exome

AF:

0.506

GnomAD4 exome

AF:

0.494

AC:

715360

AN:

1448720

Hom.:

181547

Cov.:

AF XY:

0.491

AC XY:

353605

AN XY:

720460

show subpopulations

Gnomad4 AFR exome

AF:

0.0919

Gnomad4 AMR exome

AF:

0.515

Gnomad4 ASJ exome

AF:

0.580

Gnomad4 EAS exome

AF:

0.546

Gnomad4 SAS exome

AF:

0.350

Gnomad4 FIN exome

AF:

0.460

Gnomad4 NFE exome

AF:

0.514

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.392

AC:

59553

AN:

152088

Hom.:

14215

Cov.:

AF XY:

0.391

AC XY:

29053

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.474

Gnomad4 ASJ

AF:

0.595

Gnomad4 EAS

AF:

0.544

Gnomad4 SAS

AF:

0.349

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.515

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.439

Hom.:

4298

Bravo

AF:

0.385

Asia WGS

AF:

0.404

AC:

1403

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.3

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000065

dbscSNV1_RF

Benign

0.0020

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