chr2-188993487-G-A

Variant names:

• chr2-188993487-G-A
• rs13402856
• NM_000090.4:c.1149+28G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000090.4(COL3A1):​c.1149+28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,497,954 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (9 hom., cov: 31)
  • Exomes 𝑓: 0.00046 (7 hom.)
• Consequence: COL3A1 NM_000090.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0740

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-188993487-G-A is Benign according to our data. Variant chr2-188993487-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1207155.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00521 (750/143994) while in subpopulation AFR AF = 0.0214 (731/34140). AF 95% confidence interval is 0.0201. There are 9 homozygotes in GnomAd4. There are 363 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4	c.1149+28G>A		intron_variant	Intron 16 of 50	ENST00000304636.9	NP_000081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9	c.1149+28G>A		intron_variant	Intron 16 of 50	1	NM_000090.4	ENSP00000304408.4
COL3A1	ENST00000450867.2	c.1050+547G>A		intron_variant	Intron 15 of 49	1		ENSP00000415346.2
COL3A1	ENST00000713745.1	c.1149+28G>A		intron_variant	Intron 16 of 48			ENSP00000519049.1
COL3A1	ENST00000713744.1	c.1149+28G>A		intron_variant	Intron 16 of 48			ENSP00000519048.1

Frequencies

GnomAD3 genomes AF: 0.00520 AC: 748 AN: 143882 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000942

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00151

GnomAD2 exomes AF: 0.00118 AC: 185 AN: 156804 AF XY: 0.000849

Gnomad AFR exome AF: 0.0186

Gnomad AMR exome AF: 0.000606

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000165

Gnomad OTH exome AF: 0.00112

GnomAD4 exome AF: 0.000462 AC: 626 AN: 1353960 Hom.: 7 Cov.: 23 AF XY: 0.000406 AC XY: 272 AN XY: 670250

African (AFR) AF: 0.0205 AC: 537 AN: 26160

American (AMR) AF: 0.000916 AC: 32 AN: 34950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24934

East Asian (EAS) AF: 0.00 AC: 0 AN: 35478

South Asian (SAS) AF: 0.0000257 AC: 2 AN: 77832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49308

Middle Eastern (MID) AF: 0.000869 AC: 4 AN: 4602

European-Non Finnish (NFE) AF: 0.00000574 AC: 6 AN: 1044842

Other (OTH) AF: 0.000806 AC: 45 AN: 55854

GnomAD4 genome AF: 0.00521 AC: 750 AN: 143994 Hom.: 9 Cov.: 31 AF XY: 0.00515 AC XY: 363 AN XY: 70482

African (AFR) AF: 0.0214 AC: 731 AN: 34140

American (AMR) AF: 0.000941 AC: 14 AN: 14880

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: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67802

Other (OTH) AF: 0.00150 AC: 3 AN: 2006

Alfa AF: 0.00252 Hom.: 0

Bravo AF: 0.00562

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 29, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.32
PhyloP100		-0.074
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

Publications

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Other links and lift over

dbSNP: rs13402856; hg19: chr2-189858213;