rs1552896

Variant names:

• chr9-14841389-C-G
• rs1552896
• NM_001379081.2:c.1881+58G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-14841389-C-G
• chr9-14841389-C-A
• chr9-14841389-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001379081.2(FREM1):​c.1881+58G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,381,686 control chromosomes in the GnomAD database, including 32,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2627 hom., cov: 33)
  • Exomes 𝑓: 0.21 (30014 hom.)
• Consequence: FREM1 NM_001379081.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.370
• Publications: 13 publications found

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]

FREM1 Gene-Disease associations (from GenCC):

• oculotrichoanal syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
• BNAR syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• isolated trigonocephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• trigonocephaly 2

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-14841389-C-G is Benign according to our data. Variant chr9-14841389-C-G is described in ClinVar as Benign. ClinVar VariationId is 1258834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379081.2. 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
	FREM1	NM_001379081.2	MANE Select	c.1881+58G>C		intron	N/A	NP_001366010.1	Q5H8C1-1
	FREM1	NM_144966.7		c.1881+58G>C		intron	N/A	NP_659403.4
	FREM1	NR_163238.2		n.2697+58G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FREM1	ENST00000380880.4	TSL:5 MANE Select	c.1881+58G>C		intron	N/A	ENSP00000370262.3	Q5H8C1-1
	FREM1	ENST00000380875.7	TSL:1	n.1881+58G>C		intron	N/A	ENSP00000370257.3	F8WE85
	FREM1	ENST00000895028.1		c.1881+58G>C		intron	N/A	ENSP00000565087.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25529 AN: 152058 Hom.: 2629 Cov.: 33

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.213 AC: 262402 AN: 1229510 Hom.: 30014 AF XY: 0.213 AC XY: 128360 AN XY: 603942

African (AFR) AF: 0.0569 AC: 1595 AN: 28020

American (AMR) AF: 0.152 AC: 4492 AN: 29610

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 3777 AN: 21084

East Asian (EAS) AF: 0.0285 AC: 1034 AN: 36300

South Asian (SAS) AF: 0.130 AC: 7089 AN: 54680

European-Finnish (FIN) AF: 0.218 AC: 10514 AN: 48122

Middle Eastern (MID) AF: 0.265 AC: 1335 AN: 5042

European-Non Finnish (NFE) AF: 0.233 AC: 222869 AN: 956108

Other (OTH) AF: 0.192 AC: 9697 AN: 50544

GnomAD4 genome AF: 0.168 AC: 25528 AN: 152176 Hom.: 2627 Cov.: 33 AF XY: 0.165 AC XY: 12278 AN XY: 74384

African (AFR) AF: 0.0642 AC: 2667 AN: 41540

American (AMR) AF: 0.172 AC: 2632 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3470

East Asian (EAS) AF: 0.0268 AC: 139 AN: 5184

South Asian (SAS) AF: 0.134 AC: 647 AN: 4824

European-Finnish (FIN) AF: 0.223 AC: 2357 AN: 10562

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15784 AN: 67984

Other (OTH) AF: 0.174 AC: 368 AN: 2110

Alfa AF: 0.109 Hom.: 189

Bravo AF: 0.160

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		-0.37
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: rs1552896; hg19: chr9-14841387; COSMIC: COSV66526221;