8-120147628-C-T

Variant names:

• chr8-120147628-C-T
• rs6995843
• NM_021110.4:c.-37-178C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021110.4(COL14A1):​c.-37-178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,226 control chromosomes in the GnomAD database, including 52,500 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.83 (52500 hom., cov: 33)
• Consequence: COL14A1 NM_021110.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-120147628-C-T is Benign according to our data. Variant chr8-120147628-C-T is described in ClinVar as Benign. ClinVar VariationId is 1221897.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL14A1	NM_021110.4	MANE Select	c.-37-178C>T		intron	N/A	NP_066933.1	Q05707-1
	COL14A1	NM_001413492.1		c.-37-178C>T		intron	N/A	NP_001400421.1
	COL14A1	NM_001413490.1		c.-37-178C>T		intron	N/A	NP_001400419.1	Q05707-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL14A1	ENST00000297848.8	TSL:5 MANE Select	c.-37-178C>T		intron	N/A	ENSP00000297848.3	Q05707-1
	COL14A1	ENST00000432943.6	TSL:1	n.198-178C>T		intron	N/A
	COL14A1	ENST00000498051.6	TSL:1	n.-37-178C>T		intron	N/A	ENSP00000428851.1	Q4G0W3

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125724 AN: 152108 Hom.: 52449 Cov.: 33

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.815

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.827 AC: 125829 AN: 152226 Hom.: 52500 Cov.: 33 AF XY: 0.826 AC XY: 61488 AN XY: 74408

African (AFR) AF: 0.948 AC: 39413 AN: 41568

American (AMR) AF: 0.832 AC: 12729 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2830 AN: 3470

East Asian (EAS) AF: 0.758 AC: 3929 AN: 5182

South Asian (SAS) AF: 0.721 AC: 3470 AN: 4816

European-Finnish (FIN) AF: 0.797 AC: 8433 AN: 10586

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52324 AN: 67982

Other (OTH) AF: 0.810 AC: 1715 AN: 2116

Alfa AF: 0.802 Hom.: 6133

Bravo AF: 0.839

Asia WGS AF: 0.704 AC: 2451 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.56
PhyloP100		-0.062
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: rs6995843; hg19: chr8-121159867;