chr4-143695213-A-G

Position:

• chr4-143695213-A-G

Variant summary

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

The NM_001168235.2(FREM3):​c.5185+278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,180 control chromosomes in the GnomAD database, including 5,693 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 0.25 (5693 hom., cov: 32)
• Consequence: FREM3 NM_001168235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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]

GUSBP5 (HGNC:42319): (GUSB pseudogene 5)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FREM3	NM_001168235.2	c.5185+278T>C		intron_variant		ENST00000329798.5	NP_001161707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FREM3	ENST00000329798.5	c.5185+278T>C		intron_variant		5	NM_001168235.2	ENSP00000332886	P1
GUSBP5	ENST00000641328.1	n.862-43762A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37506 AN: 152062 Hom.: 5690 Cov.: 32

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.246 AC: 37511 AN: 152180 Hom.: 5693 Cov.: 32 AF XY: 0.249 AC XY: 18529 AN XY: 74392

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.0523

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.269

Alfa AF: 0.322 Hom.: 10834

Bravo AF: 0.237

Asia WGS AF: 0.197 AC: 687 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.55

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: rs7676614; hg19: chr4-144616366;