rs9594293

chr13-38796458-G-Achr13-38796458-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
FREM2	NM_207361.6	c.6019+11650G>A		intron_variant		ENST00000280481.9
FREM2	XR_941571.3	n.6287+11650G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FREM2	ENST00000280481.9	c.6019+11650G>A		intron_variant		1	NM_207361.6	P1

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

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.205

Alfa AF: 0.173 Hom.: 4120

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

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: rs9594293; hg19: chr13-39370595;