rs34163530

Variant names:

• chr1-30716213-G-A
• rs34163530
• NM_002379.3:c.903C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-30716213-G-A
• chr1-30716213-G-C
• chr1-30716213-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002379.3(MATN1):​c.903C>T​(p.Ile301Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,614,152 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0068 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00075 (11 hom.)
• Consequence: MATN1 NM_002379.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.540
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 1-30716213-G-A is Benign according to our data. Variant chr1-30716213-G-A is described in ClinVar as Benign. ClinVar VariationId is 783930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.54 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0068 (1035/152284) while in subpopulation AFR AF = 0.0227 (942/41540). AF 95% confidence interval is 0.0215. There are 13 homozygotes in GnomAd4. There are 488 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002379.3. 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
	MATN1	NM_002379.3	MANE Select	c.903C>T	p.Ile301Ile	synonymous	Exon 5 of 8	NP_002370.1	P21941

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN1	ENST00000373765.5	TSL:1 MANE Select	c.903C>T	p.Ile301Ile	synonymous	Exon 5 of 8	ENSP00000362870.4	P21941
	MATN1	ENST00000477320.1	TSL:2	n.756C>T		non_coding_transcript_exon	Exon 3 of 3
	MATN1	ENST00000494561.1	TSL:3	n.-78C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00677 AC: 1030 AN: 152166 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00198 AC: 499 AN: 251402 AF XY: 0.00149

Gnomad AFR exome AF: 0.0253

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.000748 AC: 1094 AN: 1461868 Hom.: 11 Cov.: 35 AF XY: 0.000644 AC XY: 468 AN XY: 727232

African (AFR) AF: 0.0248 AC: 830 AN: 33480

American (AMR) AF: 0.00212 AC: 95 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1112008

Other (OTH) AF: 0.00176 AC: 106 AN: 60396

GnomAD4 genome AF: 0.00680 AC: 1035 AN: 152284 Hom.: 13 Cov.: 33 AF XY: 0.00655 AC XY: 488 AN XY: 74484

African (AFR) AF: 0.0227 AC: 942 AN: 41540

American (AMR) AF: 0.00464 AC: 71 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68022

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00218 Hom.: 3

Bravo AF: 0.00813

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

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	-0.63
CADD	Benign	1.4
DANN	Benign	0.79
PhyloP100		-0.54
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: rs34163530; hg19: chr1-31189060; COSMIC: COSV104685921; COSMIC: COSV104685921;