rs1391187

Variant names:

• chr4-143621946-G-A
• rs1391187
• NM_001168235.2:c.5654-784C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168235.2. 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
	FREM3	NM_001168235.2	MANE Select	c.5654-784C>T		intron	N/A	NP_001161707.1	P0C091

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FREM3	ENST00000329798.5	TSL:5 MANE Select	c.5654-784C>T		intron	N/A	ENSP00000332886.5	P0C091
	GUSBP5	ENST00000511042.5	TSL:5	n.192-23139G>A		intron	N/A
	GUSBP5	ENST00000641328.2		n.862+49365G>A		intron	N/A

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

African (AFR) AF: 0.563 AC: 23362 AN: 41462

American (AMR) AF: 0.450 AC: 6877 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1715 AN: 3470

East Asian (EAS) AF: 0.159 AC: 822 AN: 5168

South Asian (SAS) AF: 0.457 AC: 2202 AN: 4814

European-Finnish (FIN) AF: 0.405 AC: 4262 AN: 10530

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30817 AN: 67962

Other (OTH) AF: 0.458 AC: 967 AN: 2112

Alfa AF: 0.459 Hom.: 58613

Bravo AF: 0.474

Asia WGS AF: 0.326 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.69
DANN	Benign	0.37
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs1391187; hg19: chr4-144543099;