rs2236488

Variant names:

• chr21-46002798-C-T
• rs2236488
• NM_001848.3:c.2434+88C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-46002798-C-T
• chr21-46002798-C-A

Variant summary

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

The NM_001848.3(COL6A1):​c.2434+88C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,407,794 control chromosomes in the GnomAD database, including 195,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (19930 hom., cov: 33)
  • Exomes 𝑓: 0.52 (175285 hom.)
• Consequence: COL6A1 NM_001848.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0250
• Publications: 5 publications found

Genes affected

COL6A1 (HGNC:2211): (collagen type VI alpha 1 chain) The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy. [provided by RefSeq, Jul 2008]

COL6A1 Gene-Disease associations (from GenCC):

• Bethlem myopathy 1A

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P
• collagen 6-related myopathy

  Inheritance: SD, AD, AR Classification: DEFINITIVE Submitted by: ClinGen
• Ullrich congenital muscular dystrophy 1A

  Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Bethlem myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Ullrich congenital muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 21-46002798-C-T is Benign according to our data. Variant chr21-46002798-C-T is described in ClinVar as Benign. ClinVar VariationId is 679199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001848.3. 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
	COL6A1	NM_001848.3	MANE Select	c.2434+88C>T		intron	N/A	NP_001839.2	P12109

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A1	ENST00000361866.8	TSL:1 MANE Select	c.2434+88C>T		intron	N/A	ENSP00000355180.3	P12109
	COL6A1	ENST00000498614.5	TSL:1	n.668+88C>T		intron	N/A
	COL6A1	ENST00000866134.1		c.748+88C>T		intron	N/A	ENSP00000536193.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 76658 AN: 150186 Hom.: 19911 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.519 AC: 652694 AN: 1257494 Hom.: 175285 AF XY: 0.514 AC XY: 324022 AN XY: 629868

African (AFR) AF: 0.604 AC: 17394 AN: 28790

American (AMR) AF: 0.410 AC: 15245 AN: 37204

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 10407 AN: 24274

East Asian (EAS) AF: 0.263 AC: 9410 AN: 35836

South Asian (SAS) AF: 0.408 AC: 31776 AN: 77900

European-Finnish (FIN) AF: 0.490 AC: 19343 AN: 39464

Middle Eastern (MID) AF: 0.425 AC: 1687 AN: 3972

European-Non Finnish (NFE) AF: 0.545 AC: 521312 AN: 956518

Other (OTH) AF: 0.488 AC: 26120 AN: 53536

GnomAD4 genome AF: 0.510 AC: 76714 AN: 150300 Hom.: 19930 Cov.: 33 AF XY: 0.506 AC XY: 37161 AN XY: 73418

African (AFR) AF: 0.583 AC: 23813 AN: 40846

American (AMR) AF: 0.457 AC: 6949 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1424 AN: 3450

East Asian (EAS) AF: 0.234 AC: 1180 AN: 5048

South Asian (SAS) AF: 0.386 AC: 1827 AN: 4736

European-Finnish (FIN) AF: 0.487 AC: 5074 AN: 10428

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.520 AC: 35029 AN: 67316

Other (OTH) AF: 0.465 AC: 971 AN: 2086

Alfa AF: 0.521 Hom.: 1924

Bravo AF: 0.512

Asia WGS AF: 0.293 AC: 1016 AN: 3454

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	-0.82
CADD	Benign	5.4
DANN	Benign	0.95
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2236488; hg19: chr21-47422712; COSMIC: COSV62612817; COSMIC: COSV62612817;