1-102995952-T-A

Variant names:

• chr1-102995952-T-A
• rs2622867
• NM_001854.4:c.2295+37A>T

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.2295+37A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 1,612,872 control chromosomes in the GnomAD database, including 743,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64681 hom., cov: 33)
  • Exomes 𝑓: 0.96 (678759 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.599
• 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=-0.8).
• BP6: Variant 1-102995952-T-A is Benign according to our data. Variant chr1-102995952-T-A is described in ClinVar as Benign. ClinVar VariationId is 258443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.2295+37A>T		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.2331+37A>T		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.2178+37A>T		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.2295+37A>T		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.1947+37A>T		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000635193.1	TSL:1	n.1611+37A>T		intron	N/A	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139762 AN: 152146 Hom.: 64633 Cov.: 33

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.986

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.910

GnomAD2 exomes AF: 0.956 AC: 240007 AN: 250946 AF XY: 0.961

Gnomad AFR exome AF: 0.791

Gnomad AMR exome AF: 0.972

Gnomad ASJ exome AF: 0.896

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.970

Gnomad NFE exome AF: 0.963

Gnomad OTH exome AF: 0.951

GnomAD4 exome AF: 0.964 AC: 1407358 AN: 1460608 Hom.: 678759 Cov.: 43 AF XY: 0.965 AC XY: 701033 AN XY: 726654

African (AFR) AF: 0.787 AC: 26316 AN: 33424

American (AMR) AF: 0.969 AC: 43240 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 23391 AN: 26106

East Asian (EAS) AF: 1.00 AC: 39637 AN: 39638

South Asian (SAS) AF: 0.987 AC: 85070 AN: 86222

European-Finnish (FIN) AF: 0.970 AC: 51782 AN: 53400

Middle Eastern (MID) AF: 0.941 AC: 5294 AN: 5626

European-Non Finnish (NFE) AF: 0.967 AC: 1075097 AN: 1111220

Other (OTH) AF: 0.954 AC: 57531 AN: 60332

GnomAD4 genome AF: 0.919 AC: 139868 AN: 152264 Hom.: 64681 Cov.: 33 AF XY: 0.922 AC XY: 68624 AN XY: 74452

African (AFR) AF: 0.800 AC: 33219 AN: 41528

American (AMR) AF: 0.953 AC: 14567 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3139 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5184 AN: 5184

South Asian (SAS) AF: 0.986 AC: 4759 AN: 4828

European-Finnish (FIN) AF: 0.969 AC: 10293 AN: 10620

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65594 AN: 68026

Other (OTH) AF: 0.911 AC: 1925 AN: 2114

Alfa AF: 0.937 Hom.: 12325

Bravo AF: 0.912

Asia WGS AF: 0.983 AC: 3414 AN: 3476

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	-0.80
CADD	Benign	0.39
DANN	Benign	0.52
PhyloP100		-0.60
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: rs2622867; hg19: chr1-103461508;