rs2001185

Variant names:

• chr17-41582545-T-C
• rs2001185
• NM_000526.5:c.1322-13A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-41582545-T-C
• chr17-41582545-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000526.5(KRT14):​c.1322-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,552,686 control chromosomes in the GnomAD database, including 13,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2892 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10390 hom.)
• Consequence: KRT14 NM_000526.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -0.167
• Publications: 4 publications found

Genes affected

KRT14 (HGNC:6416): (keratin 14) This gene encodes a member of the keratin family, the most diverse group of intermediate filaments. This gene product, a type I keratin, is usually found as a heterotetramer with two keratin 5 molecules, a type II keratin. Together they form the cytoskeleton of epithelial cells. Mutations in the genes for these keratins are associated with epidermolysis bullosa simplex. At least one pseudogene has been identified at 17p12-p11. [provided by RefSeq, Jul 2008]

KRT14 Gene-Disease associations (from GenCC):

• epidermolysis bullosa simplex 1A, generalized severe

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet
• Naegeli-Franceschetti-Jadassohn syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet, Genomics England PanelApp
• epidermolysis bullosa simplex

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, Orphanet
• dermatopathia pigmentosa reticularis

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
• epidermolysis bullosa simplex 1B, generalized intermediate

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• epidermolysis bullosa simplex 1C, localized

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• epidermolysis bullosa simplex 2F, with mottled pigmentation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-41582545-T-C is Benign according to our data. Variant chr17-41582545-T-C is described in ClinVar as Benign. ClinVar VariationId is 66328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000526.5. 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
	KRT14	NM_000526.5	MANE Select	c.1322-13A>G		intron	N/A	NP_000517.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT14	ENST00000167586.7	TSL:1 MANE Select	c.1322-13A>G		intron	N/A	ENSP00000167586.6	P02533
	KRT14	ENST00000441550.2	TSL:2	n.817A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25275 AN: 151710 Hom.: 2885 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0495

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.119 AC: 19037 AN: 160610 AF XY: 0.119

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.0724

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.0604

Gnomad FIN exome AF: 0.0705

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.114 AC: 159487 AN: 1400856 Hom.: 10390 Cov.: 29 AF XY: 0.115 AC XY: 79189 AN XY: 691602

African (AFR) AF: 0.344 AC: 10930 AN: 31814

American (AMR) AF: 0.0760 AC: 2746 AN: 36116

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3826 AN: 25178

East Asian (EAS) AF: 0.0413 AC: 1493 AN: 36178

South Asian (SAS) AF: 0.143 AC: 11325 AN: 79414

European-Finnish (FIN) AF: 0.0662 AC: 3282 AN: 49592

Middle Eastern (MID) AF: 0.202 AC: 1153 AN: 5700

European-Non Finnish (NFE) AF: 0.109 AC: 117098 AN: 1078700

Other (OTH) AF: 0.131 AC: 7634 AN: 58164

GnomAD4 genome AF: 0.167 AC: 25320 AN: 151830 Hom.: 2892 Cov.: 32 AF XY: 0.164 AC XY: 12134 AN XY: 74174

African (AFR) AF: 0.332 AC: 13750 AN: 41372

American (AMR) AF: 0.0975 AC: 1487 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.0493 AC: 254 AN: 5156

South Asian (SAS) AF: 0.134 AC: 642 AN: 4794

European-Finnish (FIN) AF: 0.0747 AC: 789 AN: 10560

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7441 AN: 67910

Other (OTH) AF: 0.164 AC: 347 AN: 2110

Alfa AF: 0.140 Hom.: 343

Bravo AF: 0.177

Asia WGS AF: 0.108 AC: 375 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.37
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2001185; hg19: chr17-39738797;