NM_001854.4:c.274+42G>C

Variant names:

• chr1-103082763-C-G
• rs11164662
• NM_001854.4:c.274+42G>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.274+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,522,820 control chromosomes in the GnomAD database, including 256,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20957 hom., cov: 32)
  • Exomes 𝑓: 0.58 (235921 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0730
• Publications: 13 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=-0.83).
• BP6: Variant 1-103082763-C-G is Benign according to our data. Variant chr1-103082763-C-G is described in ClinVar as Benign. ClinVar VariationId is 258450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 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.274+42G>C		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.274+42G>C		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.274+42G>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.274+42G>C		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.274+42G>C		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000358392.6	TSL:5	c.274+42G>C		intron	N/A	ENSP00000351163.2	P12107-2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75428 AN: 151636 Hom.: 20948 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.544

GnomAD2 exomes AF: 0.592 AC: 133320 AN: 225314 AF XY: 0.598

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.654

Gnomad ASJ exome AF: 0.510

Gnomad EAS exome AF: 0.907

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.568

Gnomad OTH exome AF: 0.583

GnomAD4 exome AF: 0.580 AC: 794678 AN: 1371068 Hom.: 235921 Cov.: 21 AF XY: 0.583 AC XY: 399242 AN XY: 685176

African (AFR) AF: 0.229 AC: 6936 AN: 30306

American (AMR) AF: 0.647 AC: 28292 AN: 43706

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 13015 AN: 25440

East Asian (EAS) AF: 0.925 AC: 33984 AN: 36752

South Asian (SAS) AF: 0.682 AC: 55261 AN: 81010

European-Finnish (FIN) AF: 0.501 AC: 25717 AN: 51296

Middle Eastern (MID) AF: 0.547 AC: 2533 AN: 4634

European-Non Finnish (NFE) AF: 0.573 AC: 596434 AN: 1041090

Other (OTH) AF: 0.572 AC: 32506 AN: 56834

GnomAD4 genome AF: 0.497 AC: 75436 AN: 151752 Hom.: 20957 Cov.: 32 AF XY: 0.502 AC XY: 37238 AN XY: 74184

African (AFR) AF: 0.246 AC: 10193 AN: 41380

American (AMR) AF: 0.624 AC: 9510 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1806 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4701 AN: 5170

South Asian (SAS) AF: 0.704 AC: 3391 AN: 4820

European-Finnish (FIN) AF: 0.492 AC: 5173 AN: 10520

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38777 AN: 67840

Other (OTH) AF: 0.546 AC: 1153 AN: 2110

Alfa AF: 0.444 Hom.: 2347

Bravo AF: 0.496

Asia WGS AF: 0.768 AC: 2662 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.64
PhyloP100		0.073
PromoterAI		0.00010	Neutral
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

Other links and lift over

dbSNP: rs11164662; hg19: chr1-103548319; COSMIC: COSV62177237;