13-38766281-T-G

Position:

• chr13-38766281-T-G

Variant summary

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

The ENST00000280481.9(FREM2):​c.5410+1831T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,178 control chromosomes in the GnomAD database, including 2,145 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 (2145 hom., cov: 32)
• Consequence: FREM2 ENST00000280481.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FREM2	NM_207361.6	c.5410+1831T>G		intron_variant		ENST00000280481.9	NP_997244.4
FREM2	XR_941571.3	n.5678+1831T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FREM2	ENST00000280481.9	c.5410+1831T>G		intron_variant		1	NM_207361.6	ENSP00000280481	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24045 AN: 152058 Hom.: 2145 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.158 AC: 24050 AN: 152178 Hom.: 2145 Cov.: 32 AF XY: 0.158 AC XY: 11766 AN XY: 74400

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.150

Alfa AF: 0.168 Hom.: 2407

Bravo AF: 0.161

Asia WGS AF: 0.252 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.9
DANN	Benign	0.71

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: rs12865228; hg19: chr13-39340418;