rs7532572

Variant names:

• chr1-102985971-C-A
• rs7532572
• NM_001854.4:c.2502+1662G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-102985971-C-A
• chr1-102985971-C-G
• chr1-102985971-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001854.4(COL11A1):​c.2502+1662G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,896 control chromosomes in the GnomAD database, including 31,535 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 0.63 (31535 hom., cov: 32)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• Publications: 4 publications found

Genes affected

COL11A1 (HGNC:2186): (collagen type XI alpha 1 chain) This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Mutations in this gene are associated with type II Stickler syndrome and with Marshall syndrome. A single-nucleotide polymorphism in this gene is also associated with susceptibility to lumbar disc herniation. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]

COL11A1 Gene-Disease associations (from GenCC):

• Marshall syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• Stickler syndrome type 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Orphanet, Genomics England PanelApp
• fibrochondrogenesis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal dominant 37

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• fibrochondrogenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive Stickler syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001854.4. 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
	COL11A1	NM_001854.4	MANE Select	c.2502+1662G>T		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.2538+1662G>T		intron	N/A	NP_542196.2
	COL11A1	NM_001190709.2		c.2385+1662G>T		intron	N/A	NP_001177638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.2502+1662G>T		intron	N/A	ENSP00000359114.3
	COL11A1	ENST00000512756.5	TSL:1	c.2154+1662G>T		intron	N/A	ENSP00000426533.1
	COL11A1	ENST00000635193.1	TSL:1	n.1818+1662G>T		intron	N/A	ENSP00000489428.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95021 AN: 151778 Hom.: 31529 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.626 AC: 95061 AN: 151896 Hom.: 31535 Cov.: 32 AF XY: 0.632 AC XY: 46885 AN XY: 74232

African (AFR) AF: 0.386 AC: 16000 AN: 41398

American (AMR) AF: 0.698 AC: 10640 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3470

East Asian (EAS) AF: 0.913 AC: 4708 AN: 5156

South Asian (SAS) AF: 0.825 AC: 3975 AN: 4820

European-Finnish (FIN) AF: 0.699 AC: 7378 AN: 10562

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47627 AN: 67930

Other (OTH) AF: 0.649 AC: 1371 AN: 2114

Alfa AF: 0.604 Hom.: 3420

Bravo AF: 0.613

Asia WGS AF: 0.814 AC: 2829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.31
PhyloP100		-0.54
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs7532572; hg19: chr1-103451527;