4-143587435-T-C

Variant names:

• chr4-143587435-T-C
• rs13130123
• NM_001168235.2:c.6029-1442A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001168235.2(FREM3):​c.6029-1442A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,066 control chromosomes in the GnomAD database, including 6,880 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 0.27 (6880 hom., cov: 32)
• Consequence: FREM3 NM_001168235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

Genes affected

FREM3 (HGNC:25172): (FRAS1 related extracellular matrix 3) This gene encodes an integral membrane protein containing numerous CSPG (chondroitin sulfate proteoglycan element) repeats and Calx-beta domains. The protein belongs to the family of FRAS1/FREM extracellular matrix proteins and may play a role cell adhesion. [provided by RefSeq, Feb 2017]

ENSG00000251600 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FREM3	NM_001168235.2	c.6029-1442A>G		intron_variant	Intron 6 of 7	ENST00000329798.5	NP_001161707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FREM3	ENST00000329798.5	c.6029-1442A>G		intron_variant	Intron 6 of 7	5	NM_001168235.2	ENSP00000332886.5
ENSG00000251600	ENST00000511042.5	n.191+14854T>C		intron_variant	Intron 2 of 3	5
ENSG00000251600	ENST00000641328.1	n.861+14854T>C		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40446 AN: 151948 Hom.: 6867 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.266 AC: 40497 AN: 152066 Hom.: 6880 Cov.: 32 AF XY: 0.273 AC XY: 20259 AN XY: 74342

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.250

Alfa AF: 0.213 Hom.: 514

Bravo AF: 0.278

Asia WGS AF: 0.514 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.74

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: rs13130123; hg19: chr4-144508588;