rs2061063

Positions:

• chr4-78313433-G-C

Variant summary

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

The NM_025074.7(FRAS1):​c.1679-2161G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,204 control chromosomes in the GnomAD database, including 5,507 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 0.26 (5507 hom., cov: 31)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

Genes affected

FRAS1 (HGNC:19185): (Fraser extracellular matrix complex subunit 1) This gene encodes an extracellular matrix protein that appears to function in the regulation of epidermal-basement membrane adhesion and organogenesis during development. Mutations in this gene cause Fraser syndrome, a multisystem malformation that can include craniofacial, urogenital and respiratory system abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRAS1	NM_025074.7	c.1679-2161G>C		intron_variant		ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2	c.1679-2161G>C		intron_variant			NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4	c.1679-2161G>C		intron_variant		5	NM_025074.7	ENSP00000422834	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38652 AN: 151086 Hom.: 5508 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0796

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.256 AC: 38654 AN: 151204 Hom.: 5507 Cov.: 31 AF XY: 0.249 AC XY: 18429 AN XY: 73902

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0794

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.258

Alfa AF: 0.316 Hom.: 916

Bravo AF: 0.246

Asia WGS AF: 0.0530 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.68

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: rs2061063; hg19: chr4-79234587;