rs945748

Variant names:

• chr1-103017958-C-T
• rs945748
• NM_001854.4:c.1351-76G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-103017958-C-T
• chr1-103017958-C-G

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.1351-76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 1,160,478 control chromosomes in the GnomAD database, including 285,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (30128 hom., cov: 31)
  • Exomes 𝑓: 0.71 (255652 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.203
• Publications: 11 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), G2P, Orphanet, Genomics England PanelApp
• Stickler syndrome type 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet
• fibrochondrogenesis 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hearing loss, autosomal dominant 37

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.88).
• BP6: Variant 1-103017958-C-T is Benign according to our data. Variant chr1-103017958-C-T is described in ClinVar as Benign. ClinVar VariationId is 674750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 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.1351-76G>A		intron	N/A	NP_001845.3
	COL11A1	NM_080629.3		c.1387-76G>A		intron	N/A	NP_542196.2	P12107-2
	COL11A1	NM_001190709.2		c.1234-76G>A		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.1351-76G>A		intron	N/A	ENSP00000359114.3	P12107-1
	COL11A1	ENST00000512756.5	TSL:1	c.1003-76G>A		intron	N/A	ENSP00000426533.1	P12107-4
	COL11A1	ENST00000635193.1	TSL:1	n.667-76G>A		intron	N/A	ENSP00000489428.1	A0A0U1RRA7

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90844 AN: 151750 Hom.: 30126 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.706 AC: 712579 AN: 1008610 Hom.: 255652 AF XY: 0.712 AC XY: 371691 AN XY: 522036

African (AFR) AF: 0.278 AC: 6808 AN: 24486

American (AMR) AF: 0.693 AC: 30306 AN: 43738

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 15307 AN: 23090

East Asian (EAS) AF: 0.926 AC: 34810 AN: 37612

South Asian (SAS) AF: 0.826 AC: 63604 AN: 77018

European-Finnish (FIN) AF: 0.699 AC: 36958 AN: 52880

Middle Eastern (MID) AF: 0.653 AC: 2827 AN: 4330

European-Non Finnish (NFE) AF: 0.701 AC: 490812 AN: 700268

Other (OTH) AF: 0.689 AC: 31147 AN: 45188

GnomAD4 genome AF: 0.598 AC: 90861 AN: 151868 Hom.: 30128 Cov.: 31 AF XY: 0.605 AC XY: 44950 AN XY: 74238

African (AFR) AF: 0.289 AC: 11936 AN: 41362

American (AMR) AF: 0.688 AC: 10474 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2361 AN: 3468

East Asian (EAS) AF: 0.913 AC: 4729 AN: 5178

South Asian (SAS) AF: 0.831 AC: 4003 AN: 4818

European-Finnish (FIN) AF: 0.700 AC: 7393 AN: 10562

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47646 AN: 67926

Other (OTH) AF: 0.627 AC: 1325 AN: 2114

Alfa AF: 0.660 Hom.: 68959

Bravo AF: 0.581

Asia WGS AF: 0.814 AC: 2831 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.58
PhyloP100		-0.20
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs945748;

hg19: chr1-103483514;

COSMIC: COSV62177179;