1-30715242-C-T

Position:

• chr1-30715242-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002379.3(MATN1):​c.1275G>A​(p.Glu425=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,613,812 control chromosomes in the GnomAD database, including 98,059 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8315 hom., cov: 33)
  • Exomes 𝑓: 0.35 (89744 hom.)
• Consequence: MATN1 NM_002379.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

Genes affected

MATN1 (HGNC:6907): (matrilin 1) This gene encodes a member of von Willebrand factor A domain containing protein family. This family of proteins are thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. Mutations of this gene have been associated with variety of inherited chondrodysplasias. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.081 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN1	NM_002379.3	c.1275G>A	p.Glu425=	synonymous_variant	6/8	ENST00000373765.5	NP_002370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN1	ENST00000373765.5	c.1275G>A	p.Glu425=	synonymous_variant	6/8	1	NM_002379.3	ENSP00000362870	P1
MATN1	ENST00000494561.1	n.295G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49679 AN: 152062 Hom.: 8308 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.327

GnomAD3 exomes AF: 0.332 AC: 83345 AN: 251412 Hom.: 14370 AF XY: 0.326 AC XY: 44349 AN XY: 135886

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.166

Gnomad SAS exome AF: 0.285

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.347 AC: 507516 AN: 1461632 Hom.: 89744 Cov.: 40 AF XY: 0.344 AC XY: 250480 AN XY: 727118

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.415

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome AF: 0.327 AC: 49721 AN: 152180 Hom.: 8315 Cov.: 33 AF XY: 0.326 AC XY: 24224 AN XY: 74404

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.325

Alfa AF: 0.335 Hom.: 4681

Bravo AF: 0.320

Asia WGS AF: 0.231 AC: 803 AN: 3478

EpiCase AF: 0.331

EpiControl AF: 0.327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.1
DANN	Benign	0.69

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: rs1065755; hg19: chr1-31188089; COSMIC: COSV65650750; COSMIC: COSV65650750;