rs11164649

Variant names:

• chr1-102979123-T-G
• rs11164649
• NM_001854.4:c.2611-19A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-102979123-T-G
• chr1-102979123-T-A
• chr1-102979123-T-C

Variant summary

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

The NM_001854.4(COL11A1):​c.2611-19A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 1,611,902 control chromosomes in the GnomAD database, including 392,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (29725 hom., cov: 33)
  • Exomes 𝑓: 0.70 (362503 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.346
• Publications: 21 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Genomics England PanelApp
• Stickler syndrome type 2

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

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

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-102979123-T-G is Benign according to our data. Variant chr1-102979123-T-G is described in ClinVar as Benign. ClinVar VariationId is 258445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.891 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	NM_001854.4	MANE Select	c.2611-19A>C		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.2647-19A>C		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.2494-19A>C		intron	N/A	NP_001177638.1	P12107-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.2611-19A>C		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.2263-19A>C		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000635193.1	TSL:1	n.1943-19A>C		intron	N/A	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89671 AN: 152008 Hom.: 29722 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.620

GnomAD2 exomes AF: 0.696 AC: 174342 AN: 250312 AF XY: 0.709

Gnomad AFR exome AF: 0.245

Gnomad AMR exome AF: 0.693

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.912

Gnomad FIN exome AF: 0.698

Gnomad NFE exome AF: 0.695

Gnomad OTH exome AF: 0.691

GnomAD4 exome AF: 0.699 AC: 1020949 AN: 1459776 Hom.: 362503 Cov.: 38 AF XY: 0.704 AC XY: 511359 AN XY: 726256

African (AFR) AF: 0.243 AC: 8133 AN: 33456

American (AMR) AF: 0.689 AC: 30768 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 17373 AN: 26130

East Asian (EAS) AF: 0.925 AC: 36715 AN: 39690

South Asian (SAS) AF: 0.819 AC: 70567 AN: 86214

European-Finnish (FIN) AF: 0.698 AC: 37233 AN: 53358

Middle Eastern (MID) AF: 0.635 AC: 3661 AN: 5766

European-Non Finnish (NFE) AF: 0.698 AC: 775220 AN: 1110178

Other (OTH) AF: 0.684 AC: 41279 AN: 60306

GnomAD4 genome AF: 0.590 AC: 89687 AN: 152126 Hom.: 29725 Cov.: 33 AF XY: 0.597 AC XY: 44407 AN XY: 74394

African (AFR) AF: 0.261 AC: 10818 AN: 41492

American (AMR) AF: 0.685 AC: 10470 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2369 AN: 3468

East Asian (EAS) AF: 0.913 AC: 4714 AN: 5164

South Asian (SAS) AF: 0.824 AC: 3976 AN: 4826

European-Finnish (FIN) AF: 0.698 AC: 7391 AN: 10584

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47646 AN: 67994

Other (OTH) AF: 0.622 AC: 1314 AN: 2112

Alfa AF: 0.633 Hom.: 14154

Bravo AF: 0.572

Asia WGS AF: 0.807 AC: 2807 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	1	Fibrochondrogenesis 1 (1)
-	-	1	Hearing loss, autosomal dominant 37 (1)
-	-	1	Marshall syndrome (1)
-	-	1	Stickler syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.51
PhyloP100		0.35
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11164649;

hg19: chr1-103444679;

COSMIC: COSV62177130;