12-52544921-C-T

Position:

• chr12-52544921-C-T

Variant summary

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

The NM_033448.3(KRT71):​c.1361-178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,134 control chromosomes in the GnomAD database, including 1,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1490 hom., cov: 32)
• Consequence: KRT71 NM_033448.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.482

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-52544921-C-T is Benign according to our data. Variant chr12-52544921-C-T is described in ClinVar as [Benign]. Clinvar id is 1237503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT71	NM_033448.3	c.1361-178G>A		intron_variant		ENST00000267119.6
KRT71	XM_017018749.2	c.1115-178G>A		intron_variant
KRT71	XM_047428196.1	c.1030-572G>A		intron_variant
KRT71	XM_047428197.1	c.1235-178G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT71	ENST00000267119.6	c.1361-178G>A		intron_variant		1	NM_033448.3	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18785 AN: 152016 Hom.: 1485 Cov.: 32

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.125

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18792 AN: 152134 Hom.: 1490 Cov.: 32 AF XY: 0.127 AC XY: 9421 AN XY: 74362

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.0773

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.128

Alfa AF: 0.146 Hom.: 1617

Bravo AF: 0.107

Asia WGS AF: 0.150 AC: 524 AN: 3478

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

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.59

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: rs10506307; hg19: chr12-52938705;