rs9594293

Variant names:

• chr13-38796458-G-A
• rs9594293
• NM_207361.6:c.6019+11650G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-38796458-G-A
• chr13-38796458-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207361.6(FREM2):​c.6019+11650G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,032 control chromosomes in the GnomAD database, including 3,670 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 0.21 (3670 hom., cov: 31)
• Consequence: FREM2 NM_207361.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 5 publications found

Genes affected

FREM2 (HGNC:25396): (FRAS1 related extracellular matrix 2) This gene encodes an integral membrane protein containing numerous CSPG (chondroitin sulfate proteoglycan element) repeats and Calx-beta domains. The encoded protein localizes to the basement membrane, forming a ternary complex that plays a role in epidermal-dermal interactions. This protein is important for the integrity of skin and renal epithelia. Mutations in this gene are associated with Fraser syndrome. [provided by RefSeq, Apr 2014]

FREM2 Gene-Disease associations (from GenCC):

• Fraser syndrome 2

  Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: G2P, Ambry Genetics
• Fraser syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fraser syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FREM2	NM_207361.6	c.6019+11650G>A		intron_variant	Intron 6 of 23	ENST00000280481.9	NP_997244.4
FREM2	XR_941571.3	n.6287+11650G>A		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FREM2	ENST00000280481.9	c.6019+11650G>A		intron_variant	Intron 6 of 23	1	NM_207361.6	ENSP00000280481.7

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32139 AN: 151914 Hom.: 3668 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.212 AC: 32166 AN: 152032 Hom.: 3670 Cov.: 31 AF XY: 0.209 AC XY: 15561 AN XY: 74330

African (AFR) AF: 0.297 AC: 12299 AN: 41454

American (AMR) AF: 0.152 AC: 2327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3466

East Asian (EAS) AF: 0.292 AC: 1509 AN: 5166

South Asian (SAS) AF: 0.246 AC: 1183 AN: 4808

European-Finnish (FIN) AF: 0.157 AC: 1657 AN: 10568

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.173 AC: 11754 AN: 67968

Other (OTH) AF: 0.205 AC: 432 AN: 2108

Alfa AF: 0.182 Hom.: 10660

Bravo AF: 0.212

Asia WGS AF: 0.246 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.5
DANN	Benign	0.64
PhyloP100		0.17
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: rs9594293; hg19: chr13-39370595;