dbSNP rs11987656: COL14A1:c.349+29C>G (chr8-120162598-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021110.4(COL14A1):c.349+29C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 1,559,966 control chromosomes in the GnomAD database, including 5,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 425 hom., cov: 33)

Exomes 𝑓: 0.082 ( 5372 hom. )

Consequence

COL14A1
NM_021110.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.280

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 8-120162598-C-G is Benign according to our data. Variant chr8-120162598-C-G is described in ClinVar as Benign. ClinVar VariationId is 1252899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
COL14A1	NM_021110.4	MANE Select	c.349+29C>G	intron	N/A	NP_066933.1	Q05707-1
COL14A1	NM_001413492.1		c.349+29C>G	intron	N/A	NP_001400421.1
COL14A1	NM_001413490.1		c.349+29C>G	intron	N/A	NP_001400419.1	Q05707-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL14A1	ENST00000297848.8	TSL:5 MANE Select	c.349+29C>G	intron	N/A	ENSP00000297848.3	Q05707-1
COL14A1	ENST00000432943.6	TSL:1	n.583+29C>G	intron	N/A
COL14A1	ENST00000498051.6	TSL:1	n.349+29C>G	intron	N/A	ENSP00000428851.1	Q4G0W3

Frequencies

GnomAD3 genomes

AF:

0.0638

AC:

9713

AN:

152174

Hom.:

425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.0845

Gnomad ASJ

AF:

0.0654

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.0735

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0924

Gnomad OTH

AF:

0.0935

GnomAD2 exomes

AF:

0.0666

AC:

14272

AN:

214204

AF XY:

0.0674

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.0609

Gnomad ASJ exome

AF:

0.0826

Gnomad EAS exome

AF:

0.000122

Gnomad FIN exome

AF:

0.0747

Gnomad NFE exome

AF:

0.0949

Gnomad OTH exome

AF:

0.0771

GnomAD4 exome

AF:

0.0823

AC:

115803

AN:

1407674

Hom.:

5372

Cov.:

AF XY:

0.0804

AC XY:

56070

AN XY:

697722

show subpopulations

African (AFR)

AF:

0.0140

AC:

439

AN:

31440

American (AMR)

AF:

0.0634

AC:

2288

AN:

36116

Ashkenazi Jewish (ASJ)

AF:

0.0744

AC:

1782

AN:

23940

East Asian (EAS)

AF:

0.0000777

AC:

AN:

38608

South Asian (SAS)

AF:

0.0102

AC:

770

AN:

75180

European-Finnish (FIN)

AF:

0.0740

AC:

3837

AN:

51866

Middle Eastern (MID)

AF:

0.0586

AC:

324

AN:

5532

European-Non Finnish (NFE)

AF:

0.0938

AC:

101952

AN:

1086848

Other (OTH)

AF:

0.0758

AC:

4408

AN:

58144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

4542

9084

13627

18169

22711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3690

7380

11070

14760

18450

<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:

0.0638

AC:

9712

AN:

152292

Hom.:

425

Cov.:

AF XY:

0.0624

AC XY:

4649

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0177

AC:

736

AN:

41568

American (AMR)

AF:

0.0843

AC:

1290

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0654

AC:

227

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5196

South Asian (SAS)

AF:

0.0101

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0735

AC:

780

AN:

10614

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0924

AC:

6282

AN:

68000

Other (OTH)

AF:

0.0930

AC:

196

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

456

912

1367

1823

2279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0485

Hom.:

Bravo

AF:

0.0645

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance: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

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.1

(source)

DANN

Benign

0.19

PhyloP100

-0.28

Mutation Taster

=99/1

polymorphism (auto)

(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