rs10738377

Positions:

• chr9-14757746-C-A
• chr9-14757746-C-T

Variant summary

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

The NM_001379081.2(FREM1):​c.5335-1300G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,164 control chromosomes in the GnomAD database, including 3,278 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 0.18 (3278 hom., cov: 32)
• Consequence: FREM1 NM_001379081.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FREM1	NM_001379081.2	c.5335-1300G>T		intron_variant		ENST00000380880.4	NP_001366010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FREM1	ENST00000380880.4	c.5335-1300G>T		intron_variant		5	NM_001379081.2	ENSP00000370262	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28094 AN: 152044 Hom.: 3276 Cov.: 32

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.185 AC: 28090 AN: 152164 Hom.: 3278 Cov.: 32 AF XY: 0.182 AC XY: 13524 AN XY: 74380

Gnomad4 AFR AF: 0.0459

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.182

Alfa AF: 0.242 Hom.: 9670

Bravo AF: 0.172

Asia WGS AF: 0.215 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.66

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: rs10738377; hg19: chr9-14757744;