Genetic Variant COL14A1:p.Arg6Cys (chr8-120147858-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_021110.4(COL14A1):c.16C>T(p.Arg6Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,613,552 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00051 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

COL14A1
NM_021110.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.620

Publications

9 publications found

Variant links:

Genes affected

COL14A1 (HGNC:2191): (collagen type XIV alpha 1 chain) This gene encodes the alpha chain of type XIV collagen, a member of the FACIT (fibril-associated collagens with interrupted triple helices) collagen family. Type XIV collagen interacts with the fibril surface and is involved in the regulation of fibrillogenesis. [provided by RefSeq, Jan 2013]

COL14A1 Gene-Disease associations (from GenCC):

punctate palmoplantar keratoderma type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary palmoplantar keratoderma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

COL14A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006849587).

BP6

Variant 8-120147858-C-T is Benign according to our data. Variant chr8-120147858-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 713104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 78 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021110.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL14A1	NM_021110.4	MANE Select	c.16C>T	p.Arg6Cys	missense	Exon 2 of 48	NP_066933.1	Q05707-1
COL14A1	NM_001413492.1		c.16C>T	p.Arg6Cys	missense	Exon 2 of 48	NP_001400421.1
COL14A1	NM_001413490.1		c.16C>T	p.Arg6Cys	missense	Exon 2 of 48	NP_001400419.1	Q05707-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL14A1	ENST00000297848.8	TSL:5 MANE Select	c.16C>T	p.Arg6Cys	missense	Exon 2 of 48	ENSP00000297848.3	Q05707-1
COL14A1	ENST00000432943.6	TSL:1	n.250C>T		non_coding_transcript_exon	Exon 2 of 27
COL14A1	ENST00000498051.6	TSL:1	n.16C>T		non_coding_transcript_exon	Exon 5 of 23	ENSP00000428851.1	Q4G0W3

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000642

AC:

161

AN:

250880

AF XY:

0.000634

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00773

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000294

AC:

429

AN:

1461320

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

218

AN XY:

726946

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33458

American (AMR)

AF:

0.0000448

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00837

AC:

332

AN:

39668

South Asian (SAS)

AF:

0.000162

AC:

AN:

86168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1111750

Other (OTH)

AF:

0.000663

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000512

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41532

American (AMR)

AF:

0.000196

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0108

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000496

Hom.:

Bravo

AF:

0.000484

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000717

AC:

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.062

DEOGEN2

Benign

0.080

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.69

M_CAP

Benign

0.024

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

PhyloP100

-0.62

PrimateAI

Benign

0.28

PROVEAN

Benign

0.14

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.23

MVP

0.62

MPC

0.26

ClinPred

0.017

GERP RS

-3.2

Varity_R

0.029

gMVP

0.39

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over