rs17127270

Variant names:

• chr1-102940336-G-A
• rs17127270
• NM_001854.4:c.3375C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-102940336-G-A
• chr1-102940336-G-C
• chr1-102940336-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001854.4(COL11A1):​c.3375C>T​(p.Asp1125Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,611,018 control chromosomes in the GnomAD database, including 22,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2161 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20428 hom.)
• Consequence: COL11A1 NM_001854.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.833
• Publications: 18 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-102940336-G-A is Benign according to our data. Variant chr1-102940336-G-A is described in ClinVar as Benign. ClinVar VariationId is 258458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.833 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 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.3375C>T	p.Asp1125Asp	synonymous	Exon 43 of 67	NP_001845.3
	COL11A1	NM_080629.3		c.3411C>T	p.Asp1137Asp	synonymous	Exon 43 of 67	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.3258C>T	p.Asp1086Asp	synonymous	Exon 42 of 66	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.3375C>T	p.Asp1125Asp	synonymous	Exon 43 of 67	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.3027C>T	p.Asp1009Asp	synonymous	Exon 41 of 65	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000635193.1	TSL:1	n.*625C>T		non_coding_transcript_exon	Exon 40 of 64	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24768 AN: 151802 Hom.: 2159 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.0944

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.142

GnomAD2 exomes AF: 0.141 AC: 35409 AN: 250784 AF XY: 0.143

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.0602

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.0120

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.162 AC: 235924 AN: 1459098 Hom.: 20428 Cov.: 31 AF XY: 0.161 AC XY: 117049 AN XY: 725980

African (AFR) AF: 0.200 AC: 6692 AN: 33418

American (AMR) AF: 0.0642 AC: 2869 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3911 AN: 26110

East Asian (EAS) AF: 0.0104 AC: 414 AN: 39680

South Asian (SAS) AF: 0.140 AC: 12067 AN: 86212

European-Finnish (FIN) AF: 0.177 AC: 9470 AN: 53384

Middle Eastern (MID) AF: 0.137 AC: 787 AN: 5758

European-Non Finnish (NFE) AF: 0.172 AC: 190510 AN: 1109556

Other (OTH) AF: 0.153 AC: 9204 AN: 60284

GnomAD4 genome AF: 0.163 AC: 24795 AN: 151920 Hom.: 2161 Cov.: 32 AF XY: 0.161 AC XY: 11982 AN XY: 74246

African (AFR) AF: 0.203 AC: 8403 AN: 41396

American (AMR) AF: 0.0942 AC: 1438 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3470

East Asian (EAS) AF: 0.0157 AC: 81 AN: 5170

South Asian (SAS) AF: 0.125 AC: 604 AN: 4818

European-Finnish (FIN) AF: 0.178 AC: 1883 AN: 10552

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11349 AN: 67938

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.157 Hom.: 2595

Bravo AF: 0.157

Asia WGS AF: 0.0870 AC: 303 AN: 3478

EpiCase AF: 0.156

EpiControl AF: 0.157

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Fibrochondrogenesis 1 (2)
-	-	2	not provided (2)
-	-	2	Stickler syndrome type 2 (2)
-	-	1	Hearing loss, autosomal dominant 37 (1)
-	-	1	Marshall syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.68
DANN	Benign	0.28
PhyloP100		0.83
Mutation Taster		=88/12	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: rs17127270; hg19: chr1-103405892; COSMIC: COSV62189732;