NM_021110.4:c.1040-581T>C

Variant names:

• chr8-120206362-T-C
• rs10955961
• NM_021110.4:c.1040-581T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021110.4(COL14A1):​c.1040-581T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,896 control chromosomes in the GnomAD database, including 23,563 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23563 hom., cov: 33)
• Consequence: COL14A1 NM_021110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL14A1	NM_021110.4	c.1040-581T>C		intron_variant	Intron 9 of 47	ENST00000297848.8	NP_066933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL14A1	ENST00000297848.8	c.1040-581T>C		intron_variant	Intron 9 of 47	5	NM_021110.4	ENSP00000297848.3

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82951 AN: 151780 Hom.: 23548 Cov.: 33

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.546 AC: 82999 AN: 151896 Hom.: 23563 Cov.: 33 AF XY: 0.543 AC XY: 40319 AN XY: 74252

African (AFR) AF: 0.675 AC: 27938 AN: 41366

American (AMR) AF: 0.576 AC: 8804 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1754 AN: 3468

East Asian (EAS) AF: 0.635 AC: 3280 AN: 5164

South Asian (SAS) AF: 0.544 AC: 2621 AN: 4816

European-Finnish (FIN) AF: 0.415 AC: 4385 AN: 10554

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.477 AC: 32390 AN: 67940

Other (OTH) AF: 0.544 AC: 1146 AN: 2108

Alfa AF: 0.511 Hom.: 2539

Bravo AF: 0.569

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.57
PhyloP100		0.0
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: rs10955961; hg19: chr8-121218601;