2-188983742-T-C

Position:

• chr2-188983742-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000090.4(COL3A1):​c.80-1018T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 151,846 control chromosomes in the GnomAD database, including 11,442 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 0.35 (11442 hom., cov: 32)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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]

LOC105373791 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL3A1	NM_000090.4	c.80-1018T>C		intron_variant		ENST00000304636.9
LOC105373791	XR_007087614.1	n.109+969A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL3A1	ENST00000304636.9	c.80-1018T>C		intron_variant		1	NM_000090.4	P1
COL3A1	ENST00000450867.2	c.80-1018T>C		intron_variant		1
COL3A1	ENST00000470167.1	n.176-1018T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53816 AN: 151728 Hom.: 11440 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.354 AC: 53826 AN: 151846 Hom.: 11442 Cov.: 32 AF XY: 0.364 AC XY: 26980 AN XY: 74210

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.328

Alfa AF: 0.411 Hom.: 6001

Bravo AF: 0.337

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs2056156; hg19: chr2-189848468;