rs141241764

Variant names:

• chr2-188984794-C-G
• rs141241764
• NM_000090.4:c.114C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-188984794-C-G
• chr2-188984794-C-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_000090.4(COL3A1):​c.114C>G​(p.Ser38Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000609 in 1,613,064 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S38S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (1 hom.)
• Consequence: COL3A1 NM_000090.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.429
• Publications: 2 publications found

Genes affected

COL3A1 (HGNC:2201): (collagen type III alpha 1 chain) This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome type IV, and with aortic and arterial aneurysms. [provided by R. Dalgleish, Feb 2008]

COL3A1 Gene-Disease associations (from GenCC):

• autosomal dominant Ehlers-Danlos syndrome, vascular type

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp
• Ehlers-Danlos syndrome, vascular type

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• polymicrogyria with or without vascular-type Ehlers-Danlos syndrome

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ENSG00000304419 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 2-188984794-C-G is Benign according to our data. Variant chr2-188984794-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 199689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.429 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000533 (81/152000) while in subpopulation AMR AF = 0.00144 (22/15242). AF 95% confidence interval is 0.000977. There are 0 homozygotes in GnomAd4. There are 32 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000090.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL3A1	NM_000090.4	MANE Select	c.114C>G	p.Ser38Ser	synonymous	Exon 2 of 51	NP_000081.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL3A1	ENST00000304636.9	TSL:1 MANE Select	c.114C>G	p.Ser38Ser	synonymous	Exon 2 of 51	ENSP00000304408.4
	COL3A1	ENST00000450867.2	TSL:1	c.114C>G	p.Ser38Ser	synonymous	Exon 2 of 50	ENSP00000415346.2
	COL3A1	ENST00000713745.1		c.114C>G	p.Ser38Ser	synonymous	Exon 2 of 49	ENSP00000519049.1

Frequencies

GnomAD3 genomes AF: 0.000533 AC: 81 AN: 151882 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00145

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000751

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000331 AC: 83 AN: 250966 AF XY: 0.000317

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000635

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000617 AC: 901 AN: 1461064 Hom.: 1 Cov.: 31 AF XY: 0.000592 AC XY: 430 AN XY: 726856

African (AFR) AF: 0.000120 AC: 4 AN: 33450

American (AMR) AF: 0.000380 AC: 17 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000770 AC: 856 AN: 1111396

Other (OTH) AF: 0.000315 AC: 19 AN: 60348

GnomAD4 genome AF: 0.000533 AC: 81 AN: 152000 Hom.: 0 Cov.: 32 AF XY: 0.000431 AC XY: 32 AN XY: 74318

African (AFR) AF: 0.000121 AC: 5 AN: 41474

American (AMR) AF: 0.00144 AC: 22 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000751 AC: 51 AN: 67918

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000692 Hom.: 0

Bravo AF: 0.000563

EpiCase AF: 0.000491

EpiControl AF: 0.000593

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	Familial thoracic aortic aneurysm and aortic dissection (3)
-	-	3	not specified (3)
-	-	2	Ehlers-Danlos syndrome, type 4 (2)
-	-	1	Connective tissue disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.5
DANN	Benign	0.71
PhyloP100		-0.43
Mutation Taster		=100/0	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: rs141241764; hg19: chr2-189849520;