5-178564257-C-T

Variant names:

• chr5-178564257-C-T
• rs185493
• NM_173465.4:c.295-3509G>A

Variant summary

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

The NM_173465.4(COL23A1):​c.295-3509G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 152,034 control chromosomes in the GnomAD database, including 28,064 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 0.57 (28064 hom., cov: 31)
• Consequence: COL23A1 NM_173465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 6 publications found

Genes affected

COL23A1 (HGNC:22990): (collagen type XXIII alpha 1 chain) COL23A1 is a member of the transmembrane collagens, a subfamily of the nonfibrillar collagens that contain a single pass hydrophobic transmembrane domain (Banyard et al., 2003 [PubMed 12644459]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL23A1	NM_173465.4	c.295-3509G>A		intron_variant	Intron 1 of 28	ENST00000390654.8	NP_775736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL23A1	ENST00000390654.8	c.295-3509G>A		intron_variant	Intron 1 of 28	5	NM_173465.4	ENSP00000375069.3
COL23A1	ENST00000407622.3	c.-136-3509G>A		intron_variant	Intron 1 of 28	5		ENSP00000385092.3
COL23A1	ENST00000680889.1	n.-136-3509G>A		intron_variant	Intron 1 of 28			ENSP00000505009.1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85887 AN: 151916 Hom.: 27996 Cov.: 31

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.566 AC: 86017 AN: 152034 Hom.: 28064 Cov.: 31 AF XY: 0.569 AC XY: 42271 AN XY: 74296

African (AFR) AF: 0.883 AC: 36651 AN: 41516

American (AMR) AF: 0.588 AC: 8977 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1670 AN: 3468

East Asian (EAS) AF: 0.739 AC: 3815 AN: 5164

South Asian (SAS) AF: 0.638 AC: 3078 AN: 4824

European-Finnish (FIN) AF: 0.350 AC: 3694 AN: 10550

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26341 AN: 67932

Other (OTH) AF: 0.556 AC: 1170 AN: 2106

Alfa AF: 0.453 Hom.: 28397

Bravo AF: 0.601

Asia WGS AF: 0.689 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		-0.10
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: rs185493; hg19: chr5-177991258;