13-38686910-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_207361.6(FREM2):​c.-435C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 152,238 control chromosomes in the GnomAD database, including 298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.035 ( 298 hom., cov: 32)

Consequence

FREM2
NM_207361.6 upstream_gene

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0870
Variant links:
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]
LINC00437 (HGNC:42772): (long intergenic non-protein coding RNA 437)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 13-38686910-C-T is Benign according to our data. Variant chr13-38686910-C-T is described in ClinVar as [Benign]. Clinvar id is 1243197.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FREM2NM_207361.6 linkc.-435C>T upstream_gene_variant ENST00000280481.9 NP_997244.4 Q5SZK8-1
FREM2XM_017020554.2 linkc.-435C>T upstream_gene_variant XP_016876043.1
LINC00437NR_126377.1 linkn.-235G>A upstream_gene_variant
FREM2XR_941571.3 linkn.-167C>T upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FREM2ENST00000280481.9 linkc.-435C>T upstream_gene_variant 1 NM_207361.6 ENSP00000280481.7 Q5SZK8-1

Frequencies

GnomAD3 genomes
AF:
0.0354
AC:
5388
AN:
152120
Hom.:
298
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.123
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0147
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00955
Gnomad NFE
AF:
0.000397
Gnomad OTH
AF:
0.0225
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0355
AC:
5404
AN:
152238
Hom.:
298
Cov.:
32
AF XY:
0.0342
AC XY:
2547
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.123
Gnomad4 AMR
AF:
0.0147
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000397
Gnomad4 OTH
AF:
0.0223
Alfa
AF:
0.0178
Hom.:
36
Bravo
AF:
0.0407
Asia WGS
AF:
0.00606
AC:
22
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jun 20, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
5.6
DANN
Benign
0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2496421; hg19: chr13-39261047; API