rs4908273

Positions:

• chr1-102915573-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001854.4(COL11A1):​c.3816+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,415,680 control chromosomes in the GnomAD database, including 10,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1098 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9666 hom.)
• Consequence: COL11A1 NM_001854.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.374

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-102915573-C-T is Benign according to our data. Variant chr1-102915573-C-T is described in ClinVar as [Benign]. Clinvar id is 1221542.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL11A1	NM_001854.4	c.3816+58G>A		intron_variant		ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.3816+58G>A		intron_variant		1	NM_001854.4	P1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17465 AN: 151976 Hom.: 1096 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.117 AC: 147837 AN: 1263586 Hom.: 9666 AF XY: 0.118 AC XY: 75623 AN XY: 639404

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.0949

Gnomad4 ASJ exome AF: 0.0705

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.0578

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.115 AC: 17470 AN: 152094 Hom.: 1098 Cov.: 32 AF XY: 0.113 AC XY: 8386 AN XY: 74364

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0884

Gnomad4 ASJ AF: 0.0692

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0491

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.105

Alfa AF: 0.109 Hom.: 239

Bravo AF: 0.116

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs4908273; hg19: chr1-103381129; COSMIC: COSV62173323;