rs16932288

chr9-14791446-T-C

Variant summary

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

The NM_001379081.2(FREM1):c.3981+1297A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 152,284 control chromosomes in the GnomAD database, including 490 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 0.050 (490 hom., cov: 33)
• Consequence: FREM1 NM_001379081.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413

Genes affected

FREM1 (HGNC:23399): (FRAS1 related extracellular matrix 1) This gene encodes a basement membrane protein that may play a role in craniofacial and renal development. Mutations in this gene have been associated with bifid nose with or without anorectal and renal anomalies. Alternatively spliced transcript variants encoding different isoforms have been described. PubMed ID 19940113 describes one such variant that initiates transcription within a distinct, internal exon; the resulting shorter isoform (named Toll-like/interleukin-1 receptor regulator, TILRR) is suggested to be a co-receptor of the interleukin 1 receptor family and may regulate receptor function and Toll-like receptor/interleukin 1 receptor signal transduction, contributing to the control of inflammatory response activation. [provided by RefSeq, Apr 2011]

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 (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FREM1	NM_001379081.2	c.3981+1297A>G		intron_variant		ENST00000380880.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FREM1	ENST00000380880.4	c.3981+1297A>G		intron_variant		5	NM_001379081.2	P1
FREM1	ENST00000380875.7	c.3981+1297A>G		intron_variant, NMD_transcript_variant		1
FREM1	ENST00000466679.1	n.59+1297A>G		intron_variant, non_coding_transcript_variant		3
FREM1	ENST00000497634.2	n.142+1297A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7574 AN: 152166 Hom.: 490 Cov.: 33

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0498 AC: 7587 AN: 152284 Hom.: 490 Cov.: 33 AF XY: 0.0532 AC XY: 3964 AN XY: 74458

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0689

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0421 Hom.: 68

Bravo AF: 0.0619

Asia WGS AF: 0.123 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	9.2
Dann	Benign	0.59

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: rs16932288; hg19: chr9-14791444;