rs681387

Positions:

• chr12-52552562-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033448.3(KRT71):​c.441+75G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,442,842 control chromosomes in the GnomAD database, including 117,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15917 hom., cov: 33)
  • Exomes 𝑓: 0.39 (101344 hom.)
• Consequence: KRT71 NM_033448.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00200

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-52552562-C-G is Benign according to our data. Variant chr12-52552562-C-G is described in ClinVar as [Benign]. Clinvar id is 1290325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT71	NM_033448.3	c.441+75G>C		intron_variant		ENST00000267119.6	NP_258259.1
KRT71	XM_017018749.2	c.195+75G>C		intron_variant			XP_016874238.1
KRT71	XM_047428196.1	c.441+75G>C		intron_variant			XP_047284152.1
KRT71	XM_047428197.1	c.441+75G>C		intron_variant			XP_047284153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT71	ENST00000267119.6	c.441+75G>C		intron_variant		1	NM_033448.3	ENSP00000267119	P1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66875 AN: 152036 Hom.: 15883 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.390 AC: 503811 AN: 1290688 Hom.: 101344 AF XY: 0.393 AC XY: 251456 AN XY: 639866

Gnomad4 AFR exome AF: 0.624

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.440 AC: 66956 AN: 152154 Hom.: 15917 Cov.: 33 AF XY: 0.435 AC XY: 32329 AN XY: 74372

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.410

Alfa AF: 0.430 Hom.: 1835

Bravo AF: 0.435

Asia WGS AF: 0.350 AC: 1220 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.62

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: rs681387; hg19: chr12-52946346; COSMIC: COSV57288846;