13-38776753-A-G

Position:

• chr13-38776753-A-G

Variant summary

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

The NM_207361.6(FREM2):​c.5642-6317A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,898 control chromosomes in the GnomAD database, including 2,267 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 0.16 (2267 hom., cov: 32)
• Consequence: FREM2 NM_207361.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FREM2	NM_207361.6	c.5642-6317A>G		intron_variant		ENST00000280481.9
FREM2	XR_941571.3	n.5910-6317A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FREM2	ENST00000280481.9	c.5642-6317A>G		intron_variant		1	NM_207361.6	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24900 AN: 151784 Hom.: 2266 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.164 AC: 24909 AN: 151898 Hom.: 2267 Cov.: 32 AF XY: 0.164 AC XY: 12166 AN XY: 74248

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.154

Alfa AF: 0.157 Hom.: 400

Bravo AF: 0.167

Asia WGS AF: 0.258 AC: 894 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.48

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: rs4526895; hg19: chr13-39350890;