chr12-52544580-T-C

Position:

• chr12-52544580-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.178

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT71	NM_033448.3	c.1524A>G	p.Leu508Leu	synonymous_variant	9/9	ENST00000267119.6	NP_258259.1
KRT71	XM_047428197.1	c.1398A>G	p.Leu466Leu	synonymous_variant	8/8		XP_047284153.1
KRT71	XM_017018749.2	c.1278A>G	p.Leu426Leu	synonymous_variant	10/10		XP_016874238.1
KRT71	XM_047428196.1	c.1030-231A>G		intron_variant			XP_047284152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT71	ENST00000267119.6	c.1524A>G	p.Leu508Leu	synonymous_variant	9/9	1	NM_033448.3	ENSP00000267119.5

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58453 AN: 151884 Hom.: 13951 Cov.: 32

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

GnomAD3 exomes AF: 0.457 AC: 114963 AN: 251416 Hom.: 28524 AF XY: 0.457 AC XY: 62090 AN XY: 135884

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 SAS exome AF: 0.305

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.: 61 AF XY: 0.486 AC XY: 353061 AN XY: 727152

Gnomad4 AFR exome AF: 0.0788

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.579

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.475

GnomAD4 genome AF: 0.384 AC: 58433 AN: 152000 Hom.: 13944 Cov.: 32 AF XY: 0.384 AC XY: 28493 AN XY: 74282

Gnomad4 AFR AF: 0.0933

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.417

Alfa AF: 0.493 Hom.: 33232

Bravo AF: 0.378

Asia WGS AF: 0.357 AC: 1241 AN: 3478

EpiCase AF: 0.530

EpiControl AF: 0.525

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.74

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: rs2292507; hg19: chr12-52938364; COSMIC: COSV57291398;