rs1391187

chr4-143621946-G-A

Variant summary

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

The NM_001168235.2(FREM3):c.5654-784C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,996 control chromosomes in the GnomAD database, including 17,276 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 0.47 (17276 hom., cov: 32)
• Consequence: FREM3 NM_001168235.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FREM3	NM_001168235.2	c.5654-784C>T		intron_variant		ENST00000329798.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FREM3	ENST00000329798.5	c.5654-784C>T		intron_variant		5	NM_001168235.2	P1
GUSBP5	ENST00000641328.1	n.861+49365G>A		intron_variant, non_coding_transcript_variant
GUSBP5	ENST00000511042.5	n.192-23139G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71495 AN: 151878 Hom.: 17237 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.471 AC: 71591 AN: 151996 Hom.: 17276 Cov.: 32 AF XY: 0.469 AC XY: 34822 AN XY: 74278

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.458

Alfa AF: 0.455 Hom.: 23603

Bravo AF: 0.474

Asia WGS AF: 0.326 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.69
Dann	Benign	0.37

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: rs1391187; hg19: chr4-144543099;