8-120162598-C-T

Variant names:

• chr8-120162598-C-T
• rs11987656
• NM_021110.4:c.349+29C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_021110.4(COL14A1):​c.349+29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000994 in 1,408,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: COL14A1 NM_021110.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAdExome4 at 14 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL14A1	NM_021110.4	MANE Select	c.349+29C>T		intron	N/A	NP_066933.1	Q05707-1
	COL14A1	NM_001413492.1		c.349+29C>T		intron	N/A	NP_001400421.1
	COL14A1	NM_001413490.1		c.349+29C>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.349+29C>T		intron	N/A	ENSP00000297848.3	Q05707-1
	COL14A1	ENST00000432943.6	TSL:1	n.583+29C>T		intron	N/A
	COL14A1	ENST00000498051.6	TSL:1	n.349+29C>T		intron	N/A	ENSP00000428851.1	Q4G0W3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000280 AC: 6 AN: 214204 AF XY: 0.0000259

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000489

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000994 AC: 14 AN: 1408620 Hom.: 0 Cov.: 27 AF XY: 0.00000716 AC XY: 5 AN XY: 698172

African (AFR) AF: 0.00 AC: 0 AN: 31448

American (AMR) AF: 0.00 AC: 0 AN: 36128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23952

East Asian (EAS) AF: 0.00 AC: 0 AN: 38608

South Asian (SAS) AF: 0.0000266 AC: 2 AN: 75182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5532

European-Non Finnish (NFE) AF: 0.0000110 AC: 12 AN: 1087718

Other (OTH) AF: 0.00 AC: 0 AN: 58174

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 49

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.38
PhyloP100		-0.28

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: rs11987656; hg19: chr8-121174837;