rs6469916

Variant names:

• chr8-120320552-G-A
• rs6469916
• NM_021110.4:c.4659+4555G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-120320552-G-A
• chr8-120320552-G-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.4659+4555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 152,236 control chromosomes in the GnomAD database, including 64,687 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 0.92 (64687 hom., cov: 32)
• Consequence: COL14A1 NM_021110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• Publications: 3 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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL14A1	NM_021110.4	c.4659+4555G>A		intron_variant	Intron 40 of 47	ENST00000297848.8	NP_066933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL14A1	ENST00000297848.8	c.4659+4555G>A		intron_variant	Intron 40 of 47	5	NM_021110.4	ENSP00000297848.3
COL14A1	ENST00000309791.8	c.4659+4555G>A		intron_variant	Intron 40 of 47	5		ENSP00000311809.4

Frequencies

GnomAD3 genomes AF: 0.921 AC: 140088 AN: 152118 Hom.: 64633 Cov.: 32

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.912

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

GnomAD4 genome AF: 0.921 AC: 140203 AN: 152236 Hom.: 64687 Cov.: 32 AF XY: 0.924 AC XY: 68794 AN XY: 74436

African (AFR) AF: 0.964 AC: 40037 AN: 41546

American (AMR) AF: 0.928 AC: 14177 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3159 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5153 AN: 5182

South Asian (SAS) AF: 0.891 AC: 4297 AN: 4820

European-Finnish (FIN) AF: 0.953 AC: 10105 AN: 10602

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60255 AN: 68018

Other (OTH) AF: 0.912 AC: 1920 AN: 2106

Alfa AF: 0.891 Hom.: 52137

Bravo AF: 0.920

Asia WGS AF: 0.943 AC: 3274 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		0.48
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: rs6469916; hg19: chr8-121332791;