rs6838661

chr4-78156244-G-Cchr4-78156244-G-T

Variant summary

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

The NM_025074.7(FRAS1):c.109-81266G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,066 control chromosomes in the GnomAD database, including 2,060 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 (2060 hom., cov: 32)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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 = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRAS1	NM_025074.7	c.109-81266G>C		intron_variant		ENST00000512123.4
FRAS1	NM_001166133.2	c.109-81266G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRAS1	ENST00000512123.4	c.109-81266G>C		intron_variant		5	NM_025074.7	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23863 AN: 151954 Hom.: 2062 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.157 AC: 23863 AN: 152066 Hom.: 2060 Cov.: 32 AF XY: 0.154 AC XY: 11478 AN XY: 74318

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.0529

Gnomad4 SAS AF: 0.0714

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.151

Alfa AF: 0.172 Hom.: 292

Bravo AF: 0.150

Asia WGS AF: 0.0740 AC: 260 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	4.9
Dann	Benign	0.66

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: rs6838661; hg19: chr4-79077398;