rs71664954

Variant names:

• chr1-103004433-A-G
• rs71664954
• NM_001854.4:c.1944+11T>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.1944+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 1,602,428 control chromosomes in the GnomAD database, including 783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (62 hom., cov: 32)
  • Exomes 𝑓: 0.028 (721 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.414
• Publications: 5 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), Genomics England PanelApp, Orphanet, G2P
• Stickler syndrome type 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P
• 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 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=-0.64).
• BP6: Variant 1-103004433-A-G is Benign according to our data. Variant chr1-103004433-A-G is described in ClinVar as Benign. ClinVar VariationId is 195479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0607 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.1944+11T>C		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.1980+11T>C		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.1827+11T>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.1944+11T>C		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.1596+11T>C		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000635193.1	TSL:1	n.1260+11T>C		intron	N/A	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3660 AN: 152118 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.0664

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.0299 AC: 7464 AN: 249280 AF XY: 0.0321

Gnomad AFR exome AF: 0.0128

Gnomad AMR exome AF: 0.0157

Gnomad ASJ exome AF: 0.0435

Gnomad EAS exome AF: 0.0746

Gnomad FIN exome AF: 0.00315

Gnomad NFE exome AF: 0.0283

Gnomad OTH exome AF: 0.0283

GnomAD4 exome AF: 0.0281 AC: 40759 AN: 1450192 Hom.: 721 Cov.: 29 AF XY: 0.0290 AC XY: 20909 AN XY: 721976

African (AFR) AF: 0.0142 AC: 471 AN: 33176

American (AMR) AF: 0.0165 AC: 737 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 1114 AN: 25984

East Asian (EAS) AF: 0.0592 AC: 2340 AN: 39540

South Asian (SAS) AF: 0.0490 AC: 4196 AN: 85644

European-Finnish (FIN) AF: 0.00420 AC: 224 AN: 53284

Middle Eastern (MID) AF: 0.0424 AC: 204 AN: 4806

European-Non Finnish (NFE) AF: 0.0269 AC: 29698 AN: 1103248

Other (OTH) AF: 0.0296 AC: 1775 AN: 59870

GnomAD4 genome AF: 0.0241 AC: 3672 AN: 152236 Hom.: 62 Cov.: 32 AF XY: 0.0240 AC XY: 1785 AN XY: 74432

African (AFR) AF: 0.0145 AC: 602 AN: 41562

American (AMR) AF: 0.0272 AC: 416 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3468

East Asian (EAS) AF: 0.0665 AC: 345 AN: 5186

South Asian (SAS) AF: 0.0536 AC: 259 AN: 4828

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10614

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0262 AC: 1783 AN: 67994

Other (OTH) AF: 0.0289 AC: 61 AN: 2110

Alfa AF: 0.0263 Hom.: 17

Bravo AF: 0.0251

Asia WGS AF: 0.0440 AC: 151 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	not provided (2)
-	-	1	Fibrochondrogenesis 1 (1)
-	-	1	Stickler syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.41
Mutation Taster		=99/1	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: rs71664954; hg19: chr1-103469989;