rs116303092

Variant names:

• chr1-103074602-T-C
• rs116303092
• NM_001854.4:c.651+16A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-103074602-T-C
• chr1-103074602-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001854.4(COL11A1):​c.651+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,612,216 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (42 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (51 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.411
• Publications: 1 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=-0.86).
• BP6: Variant 1-103074602-T-C is Benign according to our data. Variant chr1-103074602-T-C is described in ClinVar as Benign. ClinVar VariationId is 258473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0144 (2195/152180) while in subpopulation AFR AF = 0.0503 (2088/41532). AF 95% confidence interval is 0.0485. There are 42 homozygotes in GnomAd4. There are 1048 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 AR,AD gene

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.651+16A>G		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.651+16A>G		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.651+16A>G		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.651+16A>G		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.651+16A>G		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000358392.6	TSL:5	c.651+16A>G		intron	N/A	ENSP00000351163.2	P12107-2

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2186 AN: 152062 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00538

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00909

GnomAD2 exomes AF: 0.00384 AC: 960 AN: 250248 AF XY: 0.00282

Gnomad AFR exome AF: 0.0527

Gnomad AMR exome AF: 0.00242

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00247

GnomAD4 exome AF: 0.00144 AC: 2100 AN: 1460036 Hom.: 51 Cov.: 31 AF XY: 0.00127 AC XY: 922 AN XY: 726372

African (AFR) AF: 0.0508 AC: 1697 AN: 33406

American (AMR) AF: 0.00290 AC: 129 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53044

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5752

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1111028

Other (OTH) AF: 0.00355 AC: 214 AN: 60314

GnomAD4 genome AF: 0.0144 AC: 2195 AN: 152180 Hom.: 42 Cov.: 32 AF XY: 0.0141 AC XY: 1048 AN XY: 74394

African (AFR) AF: 0.0503 AC: 2088 AN: 41532

American (AMR) AF: 0.00537 AC: 82 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67982

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.00395 Hom.: 4

Bravo AF: 0.0164

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Intervertebral disc disorder;C0265235:Marshall syndrome;C1858084:Stickler syndrome type 2;C3278138:Fibrochondrogenesis 1;C4760307:Hearing loss, autosomal dominant 37 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.40
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism

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: rs116303092; hg19: chr1-103540158;