rs115628315

Variant names:

• chr20-45298166-C-G
• rs115628315
• NM_001393530.1:c.1426+4G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-45298166-C-G
• chr20-45298166-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_001393530.1(MATN4):​c.1426+4G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000364 in 1,595,424 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: MATN4 NM_001393530.1 splice_region, intron
• Scores: Splicing: ADA: 0.00004307
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.08
• Publications: 0 publications found

Genes affected

MATN4 (HGNC:6910): (matrilin 4) This gene encodes a member of von Willebrand factor A domain-containing protein family. The proteins of this family are thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This family member is thought to be play a role in reorganizing and regenerating the corneal matrix in granular and lattice type I dystrophies. It may also be involved in wound healing in the dentin-pulp complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 20-45298166-C-G is Benign according to our data. Variant chr20-45298166-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3037464.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393530.1. 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
	MATN4	NM_001393530.1	MANE Select	c.1426+4G>C		splice_region intron	N/A	NP_001380459.1	O95460-2
	MATN4	NM_003833.5		c.1426+4G>C		splice_region intron	N/A	NP_003824.2
	MATN4	NM_001393531.1		c.1426+4G>C		splice_region intron	N/A	NP_001380460.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN4	ENST00000372756.6	TSL:1 MANE Select	c.1426+4G>C		splice_region intron	N/A	ENSP00000361842.1	O95460-2
	MATN4	ENST00000372754.5	TSL:5	c.1549+4G>C		splice_region intron	N/A	ENSP00000361840.1	O95460-1
	MATN4	ENST00000360607.10	TSL:1	c.1303+4G>C		splice_region intron	N/A	ENSP00000353819.5	O95460-4

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 260 AN: 152190 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00594

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000498 AC: 120 AN: 241164 AF XY: 0.000368

Gnomad AFR exome AF: 0.00678

Gnomad AMR exome AF: 0.000323

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.000217 AC: 313 AN: 1443116 Hom.: 1 Cov.: 33 AF XY: 0.000153 AC XY: 109 AN XY: 714336

African (AFR) AF: 0.00724 AC: 240 AN: 33168

American (AMR) AF: 0.000340 AC: 15 AN: 44076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25400

East Asian (EAS) AF: 0.00 AC: 0 AN: 39266

South Asian (SAS) AF: 0.0000705 AC: 6 AN: 85132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52212

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5694

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1098704

Other (OTH) AF: 0.000824 AC: 49 AN: 59464

GnomAD4 genome AF: 0.00175 AC: 267 AN: 152308 Hom.: 1 Cov.: 32 AF XY: 0.00172 AC XY: 128 AN XY: 74486

African (AFR) AF: 0.00609 AC: 253 AN: 41570

American (AMR) AF: 0.000653 AC: 10 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.00220

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MATN4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.58
PhyloP100		-1.1
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000043
dbscSNV1_RF	Benign	0.030
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: rs115628315; hg19: chr20-43926806;