rs186245518

Variant names:

• chr1-102913704-T-A
• rs186245518
• NM_001854.4:c.3979-14A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-102913704-T-A
• chr1-102913704-T-C

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.3979-14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,611,876 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (62 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -6.74
• 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• Stickler syndrome type 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Orphanet, Genomics England PanelApp
• 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 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=-0.93).
• BP6: Variant 1-102913704-T-A is Benign according to our data. Variant chr1-102913704-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00404 (615/152178) while in subpopulation SAS AF = 0.0127 (61/4818). AF 95% confidence interval is 0.0101. There are 3 homozygotes in GnomAd4. There are 282 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	NM_001854.4	MANE Select	c.3979-14A>T		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.4015-14A>T		intron	N/A	NP_542196.2
	COL11A1	NM_001190709.2		c.3862-14A>T		intron	N/A	NP_001177638.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL11A1	ENST00000370096.9	TSL:1 MANE Select	c.3979-14A>T		intron	N/A	ENSP00000359114.3
	COL11A1	ENST00000512756.5	TSL:1	c.3631-14A>T		intron	N/A	ENSP00000426533.1
	COL11A1	ENST00000635193.1	TSL:1	n.*1229-14A>T		intron	N/A	ENSP00000489428.1

Frequencies

GnomAD3 genomes AF: 0.00405 AC: 616 AN: 152058 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00653

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00521 AC: 1310 AN: 251270 AF XY: 0.00599

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.00617

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00640 AC: 9344 AN: 1459698 Hom.: 62 Cov.: 29 AF XY: 0.00662 AC XY: 4809 AN XY: 726338

African (AFR) AF: 0.000868 AC: 29 AN: 33402

American (AMR) AF: 0.00110 AC: 49 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00276 AC: 72 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.0151 AC: 1302 AN: 86206

European-Finnish (FIN) AF: 0.00305 AC: 163 AN: 53406

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5760

European-Non Finnish (NFE) AF: 0.00655 AC: 7268 AN: 1110286

Other (OTH) AF: 0.00733 AC: 442 AN: 60296

GnomAD4 genome AF: 0.00404 AC: 615 AN: 152178 Hom.: 3 Cov.: 32 AF XY: 0.00379 AC XY: 282 AN XY: 74414

African (AFR) AF: 0.00108 AC: 45 AN: 41524

American (AMR) AF: 0.00209 AC: 32 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0127 AC: 61 AN: 4818

European-Finnish (FIN) AF: 0.00189 AC: 20 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00653 AC: 444 AN: 67984

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00216 Hom.: 1

Bravo AF: 0.00354

Asia WGS AF: 0.00404 AC: 14 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	1	Fibrochondrogenesis 1 (1)
-	-	1	Stickler syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0020
DANN	Benign	0.40
PhyloP100		-6.7
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: rs186245518; hg19: chr1-103379260;