rs4729131

Variant names:

• chr7-94399115-G-A
• rs4729131
• NM_000089.4:c.132+31G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-94399115-G-A
• chr7-94399115-G-C

Variant summary

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

The NM_000089.4(COL1A2):​c.132+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,598,662 control chromosomes in the GnomAD database, including 26,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2384 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24022 hom.)
• Consequence: COL1A2 NM_000089.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0210

Genes affected

COL1A2 (HGNC:2198): (collagen type I alpha 2 chain) This gene encodes the pro-alpha2 chain of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIB, recessive Ehlers-Danlos syndrome Classical type, idiopathic osteoporosis, and atypical Marfan syndrome. Symptoms associated with mutations in this gene, however, tend to be less severe than mutations in the gene for the alpha1 chain of type I collagen (COL1A1) reflecting the different role of alpha2 chains in matrix integrity. Three transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-94399115-G-A is Benign according to our data. Variant chr7-94399115-G-A is described in ClinVar as [Benign]. Clinvar id is 1271287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL1A2	NM_000089.4	c.132+31G>A		intron_variant	Intron 4 of 51	ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11	c.132+31G>A		intron_variant	Intron 4 of 51	1	NM_000089.4	ENSP00000297268.6

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25424 AN: 151908 Hom.: 2387 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.192 AC: 48247 AN: 251194 AF XY: 0.198

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.277

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.178 AC: 256870 AN: 1446636 Hom.: 24022 Cov.: 28 AF XY: 0.181 AC XY: 130559 AN XY: 720626

African (AFR) AF: 0.105 AC: 3472 AN: 33166

American (AMR) AF: 0.125 AC: 5596 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4781 AN: 26016

East Asian (EAS) AF: 0.264 AC: 10439 AN: 39572

South Asian (SAS) AF: 0.244 AC: 20965 AN: 85820

European-Finnish (FIN) AF: 0.275 AC: 14657 AN: 53382

Middle Eastern (MID) AF: 0.160 AC: 920 AN: 5746

European-Non Finnish (NFE) AF: 0.169 AC: 185329 AN: 1098396

Other (OTH) AF: 0.179 AC: 10711 AN: 59880

GnomAD4 genome AF: 0.167 AC: 25411 AN: 152026 Hom.: 2384 Cov.: 32 AF XY: 0.173 AC XY: 12884 AN XY: 74294

African (AFR) AF: 0.109 AC: 4527 AN: 41486

American (AMR) AF: 0.148 AC: 2259 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1371 AN: 5180

South Asian (SAS) AF: 0.245 AC: 1178 AN: 4816

European-Finnish (FIN) AF: 0.288 AC: 3039 AN: 10556

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11908 AN: 67938

Other (OTH) AF: 0.155 AC: 326 AN: 2108

Alfa AF: 0.171 Hom.: 9048

Bravo AF: 0.152

Asia WGS AF: 0.218 AC: 758 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.72
PhyloP100		0.021
Mutation Taster		=100/0	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

Publications

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Other links and lift over

dbSNP: rs4729131; hg19: chr7-94028427; COSMIC: COSV51958701; COSMIC: COSV51958701;