chr13-38746624-A-G

Variant names:

• chr13-38746624-A-G
• rs1037254
• NM_207361.6:c.5264-17680A>G

Variant summary

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

The ENST00000280481.9(FREM2):​c.5264-17680A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,002 control chromosomes in the GnomAD database, including 23,026 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 0.52 (23026 hom., cov: 31)
• Consequence: FREM2 ENST00000280481.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000280481.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FREM2	NM_207361.6	MANE Select	c.5264-17680A>G		intron	N/A	NP_997244.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FREM2	ENST00000280481.9	TSL:1 MANE Select	c.5264-17680A>G		intron	N/A	ENSP00000280481.7

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78642 AN: 151884 Hom.: 23013 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.518 AC: 78683 AN: 152002 Hom.: 23026 Cov.: 31 AF XY: 0.522 AC XY: 38814 AN XY: 74312

African (AFR) AF: 0.233 AC: 9659 AN: 41460

American (AMR) AF: 0.612 AC: 9342 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1868 AN: 3472

East Asian (EAS) AF: 0.496 AC: 2553 AN: 5142

South Asian (SAS) AF: 0.437 AC: 2107 AN: 4818

European-Finnish (FIN) AF: 0.745 AC: 7875 AN: 10568

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43356 AN: 67974

Other (OTH) AF: 0.518 AC: 1092 AN: 2110

Alfa AF: 0.592 Hom.: 13623

Bravo AF: 0.499

Asia WGS AF: 0.468 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.73
DANN	Benign	0.67
PhyloP100		-0.18
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: rs1037254; hg19: chr13-39320761;