8-120168425-G-A

Variant names:

• chr8-120168425-G-A
• rs56122736
• NM_021110.4:c.436+178G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021110.4(COL14A1):​c.436+178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,942 control chromosomes in the GnomAD database, including 5,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.22 (5364 hom., cov: 32)
• Consequence: COL14A1 NM_021110.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.345
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-120168425-G-A is Benign according to our data. Variant chr8-120168425-G-A is described in ClinVar as Benign. ClinVar VariationId is 1224105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 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.436+178G>A		intron	N/A	NP_066933.1	Q05707-1
	COL14A1	NM_001413492.1		c.436+178G>A		intron	N/A	NP_001400421.1
	COL14A1	NM_001413490.1		c.436+178G>A		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.436+178G>A		intron	N/A	ENSP00000297848.3	Q05707-1
	COL14A1	ENST00000432943.6	TSL:1	n.670+178G>A		intron	N/A
	COL14A1	ENST00000498051.6	TSL:1	n.436+178G>A		intron	N/A	ENSP00000428851.1	Q4G0W3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32783 AN: 151824 Hom.: 5347 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.216 AC: 32850 AN: 151942 Hom.: 5364 Cov.: 32 AF XY: 0.214 AC XY: 15884 AN XY: 74278

African (AFR) AF: 0.457 AC: 18931 AN: 41406

American (AMR) AF: 0.162 AC: 2478 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3470

East Asian (EAS) AF: 0.161 AC: 831 AN: 5154

South Asian (SAS) AF: 0.224 AC: 1074 AN: 4792

European-Finnish (FIN) AF: 0.0774 AC: 817 AN: 10562

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7563 AN: 67972

Other (OTH) AF: 0.203 AC: 428 AN: 2112

Alfa AF: 0.144 Hom.: 478

Bravo AF: 0.231

Asia WGS AF: 0.228 AC: 793 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.91
DANN	Benign	0.49
PhyloP100		-0.34
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: rs56122736; hg19: chr8-121180664;