rs681387

Variant names:

• chr12-52552562-C-G
• rs681387
• NM_033448.3:c.441+75G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• isolated familial wooly hair disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypotrichosis 13

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033448.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT71	NM_033448.3	MANE Select	c.441+75G>C		intron	N/A	NP_258259.1	Q3SY84

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT71	ENST00000267119.6	TSL:1 MANE Select	c.441+75G>C		intron	N/A	ENSP00000267119.5	Q3SY84

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

African (AFR) AF: 0.624 AC: 17804 AN: 28544

American (AMR) AF: 0.225 AC: 7236 AN: 32174

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 7691 AN: 20290

East Asian (EAS) AF: 0.175 AC: 6765 AN: 38730

South Asian (SAS) AF: 0.456 AC: 31934 AN: 70032

European-Finnish (FIN) AF: 0.384 AC: 19417 AN: 50500

Middle Eastern (MID) AF: 0.345 AC: 1637 AN: 4746

European-Non Finnish (NFE) AF: 0.393 AC: 389949 AN: 991664

Other (OTH) AF: 0.396 AC: 21378 AN: 54008

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

African (AFR) AF: 0.617 AC: 25625 AN: 41506

American (AMR) AF: 0.300 AC: 4593 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3470

East Asian (EAS) AF: 0.178 AC: 919 AN: 5176

South Asian (SAS) AF: 0.451 AC: 2173 AN: 4814

European-Finnish (FIN) AF: 0.387 AC: 4097 AN: 10590

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26898 AN: 67990

Other (OTH) AF: 0.410 AC: 865 AN: 2112

Alfa AF: 0.430 Hom.: 1835

Bravo AF: 0.435

Asia WGS AF: 0.350 AC: 1220 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.62
PhyloP100		-0.0020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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