12-52545441-G-A

Position:

• chr12-52545441-G-A

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.1360+124C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 590,764 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (114 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (33 hom.)
• Consequence: KRT71 NM_033448.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.26

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=-0.5).
• BP6: Variant 12-52545441-G-A is Benign according to our data. Variant chr12-52545441-G-A is described in ClinVar as [Benign]. Clinvar id is 1253700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT71	NM_033448.3	c.1360+124C>T		intron_variant		ENST00000267119.6	NP_258259.1
KRT71	XM_017018749.2	c.1114+124C>T		intron_variant			XP_016874238.1
KRT71	XM_047428196.1	c.1030-1092C>T		intron_variant			XP_047284152.1
KRT71	XM_047428197.1	c.1234+124C>T		intron_variant			XP_047284153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT71	ENST00000267119.6	c.1360+124C>T		intron_variant		1	NM_033448.3	ENSP00000267119	P1

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3343 AN: 152176 Hom.: 113 Cov.: 33

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00311 AC: 1363 AN: 438470 Hom.: 33 AF XY: 0.00266 AC XY: 610 AN XY: 229672

Gnomad4 AFR exome AF: 0.0778

Gnomad4 AMR exome AF: 0.00597

Gnomad4 ASJ exome AF: 0.00496

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000248

Gnomad4 FIN exome AF: 0.0000464

Gnomad4 NFE exome AF: 0.000694

Gnomad4 OTH exome AF: 0.00699

GnomAD4 genome AF: 0.0220 AC: 3353 AN: 152294 Hom.: 114 Cov.: 33 AF XY: 0.0211 AC XY: 1574 AN XY: 74466

Gnomad4 AFR AF: 0.0741

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0180 Hom.: 8

Bravo AF: 0.0257

Asia WGS AF: 0.00693 AC: 24 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	clinical testing	GeneDx	Jun 21, 2021	- -
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	-0.50
CADD	Benign	11
DANN	Benign	0.72

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: rs60971309; hg19: chr12-52939225;