NM_001278298.2:c.7765G>A

Variant names:

• chr3-130471872-G-A
• rs73868680
• NM_001278298.2:c.7765G>A

Variant summary

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

The NM_001278298.2(COL6A5):​c.7765G>A​(p.Ala2589Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 1,468,390 control chromosomes in the GnomAD database, including 4,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (1208 hom., cov: 23)
  • Exomes 𝑓: 0.065 (3727 hom.)
• Consequence: COL6A5 NM_001278298.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.413
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006091118).
• BP6: Variant 3-130471872-G-A is Benign according to our data. Variant chr3-130471872-G-A is described in ClinVar as Benign. ClinVar VariationId is 402555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

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.7765G>A	p.Ala2589Thr	missense	Exon 40 of 41	NP_001265227.1	H0Y393
	COL6A5	NM_153264.7		c.7574+905G>A		intron	N/A	NP_694996.5
	COL6A5	NR_022012.3		n.8103G>A		non_coding_transcript_exon	Exon 40 of 42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A5	ENST00000373157.9	TSL:2 MANE Select	c.7765G>A	p.Ala2589Thr	missense	Exon 40 of 41	ENSP00000362250.5	H0Y393
	COL6A5	ENST00000312481.11	TSL:1	n.7765G>A		non_coding_transcript_exon	Exon 40 of 42	ENSP00000309762.7	A8TX70-1
	COL6A5	ENST00000512482.1	TSL:5	c.1270G>A	p.Ala424Thr	missense	Exon 5 of 6	ENSP00000424968.1	H0Y9T2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 15824 AN: 85468 Hom.: 1203 Cov.: 23

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0741

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0476

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.164 AC: 11817 AN: 72030 AF XY: 0.164

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.0716

Gnomad FIN exome AF: 0.0461

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.0647 AC: 89457 AN: 1382786 Hom.: 3727 Cov.: 41 AF XY: 0.0657 AC XY: 44850 AN XY: 682376

African (AFR) AF: 0.217 AC: 6843 AN: 31534

American (AMR) AF: 0.122 AC: 4348 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.0618 AC: 1553 AN: 25148

East Asian (EAS) AF: 0.0438 AC: 1565 AN: 35698

South Asian (SAS) AF: 0.118 AC: 9319 AN: 79200

European-Finnish (FIN) AF: 0.0210 AC: 710 AN: 33884

Middle Eastern (MID) AF: 0.0857 AC: 487 AN: 5682

European-Non Finnish (NFE) AF: 0.0558 AC: 60149 AN: 1078110

Other (OTH) AF: 0.0775 AC: 4483 AN: 57844

GnomAD4 genome AF: 0.185 AC: 15859 AN: 85604 Hom.: 1208 Cov.: 23 AF XY: 0.180 AC XY: 7537 AN XY: 41830

African (AFR) AF: 0.243 AC: 9075 AN: 37366

American (AMR) AF: 0.169 AC: 1469 AN: 8692

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 205 AN: 1560

East Asian (EAS) AF: 0.0742 AC: 301 AN: 4054

South Asian (SAS) AF: 0.185 AC: 544 AN: 2940

European-Finnish (FIN) AF: 0.0476 AC: 191 AN: 4010

Middle Eastern (MID) AF: 0.200 AC: 26 AN: 130

European-Non Finnish (NFE) AF: 0.148 AC: 3735 AN: 25234

Other (OTH) AF: 0.162 AC: 201 AN: 1240

Alfa AF: 0.147 Hom.: 410

Bravo AF: 0.116

ExAC AF: 0.159 AC: 1354

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-0.45	T
PhyloP100		0.41
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.18
Sift	Benign	0.13	T
Sift4G	Uncertain	0.023	D
Vest4		0.080
MPC		0.051
ClinPred		0.0047	T
GERP RS		1.2
gMVP		0.054
Mutation Taster		=99/1	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: rs73868680; hg19: chr3-130190716; COSMIC: COSV55194260;