rs10518194

chr4-78162336-A-G

Variant summary

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

The NM_025074.7(FRAS1):c.109-75174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,138 control chromosomes in the GnomAD database, including 2,245 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 0.17 (2245 hom., cov: 32)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRAS1	NM_025074.7	c.109-75174A>G		intron_variant		ENST00000512123.4
FRAS1	NM_001166133.2	c.109-75174A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRAS1	ENST00000512123.4	c.109-75174A>G		intron_variant		5	NM_025074.7	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25316 AN: 152020 Hom.: 2247 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.0729

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.166 AC: 25321 AN: 152138 Hom.: 2245 Cov.: 32 AF XY: 0.164 AC XY: 12177 AN XY: 74360

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0525

Gnomad4 SAS AF: 0.0723

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.158

Alfa AF: 0.181 Hom.: 4187

Bravo AF: 0.161

Asia WGS AF: 0.0760 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.8
Dann	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10518194; hg19: chr4-79083490;