NM_001278298.2:c.480C>T

Variant names:

• chr3-130376649-C-T
• rs6787083
• NM_001278298.2:c.480C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001278298.2(COL6A5):​c.480C>T​(p.Asp160Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,612,892 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (29 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (33 hom.)
• Consequence: COL6A5 NM_001278298.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.38
• Publications: 0 publications found

Genes affected

COL6A5 (HGNC:26674): (collagen type VI alpha 5 chain) This gene encodes a member of the collagen superfamily of proteins. The encoded protein contains multiple von Willebrand factor A-like domains and may interact with the alpha 1 and alpha 2 chains of collagen VI to form the complete collagen VI trimer. Polymorphisms in this gene may be linked to dermal phenotypes, such as eczema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-130376649-C-T is Benign according to our data. Variant chr3-130376649-C-T is described in ClinVar as Benign. ClinVar VariationId is 771353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.38 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0114 (1729/152214) while in subpopulation AFR AF = 0.0392 (1630/41538). AF 95% confidence interval is 0.0377. There are 29 homozygotes in GnomAd4. There are 802 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278298.2. 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
	COL6A5	NM_001278298.2	MANE Select	c.480C>T	p.Asp160Asp	synonymous	Exon 3 of 41	NP_001265227.1	H0Y393
	COL6A5	NM_153264.7		c.480C>T	p.Asp160Asp	synonymous	Exon 3 of 40	NP_694996.5
	COL6A5	NR_022012.3		n.818C>T		non_coding_transcript_exon	Exon 3 of 42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A5	ENST00000373157.9	TSL:2 MANE Select	c.480C>T	p.Asp160Asp	synonymous	Exon 3 of 41	ENSP00000362250.5	H0Y393
	COL6A5	ENST00000312481.11	TSL:1	n.480C>T		non_coding_transcript_exon	Exon 3 of 42	ENSP00000309762.7	A8TX70-1
	COL6A5	ENST00000512836.6	TSL:2	c.480C>T	p.Asp160Asp	synonymous	Exon 3 of 40	ENSP00000422898.2	A8TX70-2

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1722 AN: 152096 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0392

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00365 AC: 899 AN: 246362 AF XY: 0.00285

Gnomad AFR exome AF: 0.0426

Gnomad AMR exome AF: 0.00680

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000562

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000360

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00132 AC: 1925 AN: 1460678 Hom.: 33 Cov.: 32 AF XY: 0.00115 AC XY: 836 AN XY: 726550

African (AFR) AF: 0.0439 AC: 1470 AN: 33448

American (AMR) AF: 0.00595 AC: 265 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39648

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111362

Other (OTH) AF: 0.00249 AC: 150 AN: 60326

GnomAD4 genome AF: 0.0114 AC: 1729 AN: 152214 Hom.: 29 Cov.: 32 AF XY: 0.0108 AC XY: 802 AN XY: 74432

African (AFR) AF: 0.0392 AC: 1630 AN: 41538

American (AMR) AF: 0.00497 AC: 76 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68006

Other (OTH) AF: 0.00569 AC: 12 AN: 2110

Alfa AF: 0.00570 Hom.: 10

Bravo AF: 0.0130

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.85
CADD	Benign	0.95
DANN	Benign	0.20
PhyloP100		-3.4
Mutation Taster		=98/2	polymorphism

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: rs6787083; hg19: chr3-130095492; COSMIC: COSV55199439;