rs1268789

Positions:

• chr4-78359539-T-C
• chr4-78359539-T-G

Variant summary

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

The NM_025074.7(FRAS1):​c.2423-3974T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,772 control chromosomes in the GnomAD database, including 32,134 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 0.64 (32134 hom., cov: 30)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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 = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRAS1	NM_025074.7	c.2423-3974T>C		intron_variant		ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2	c.2423-3974T>C		intron_variant			NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4	c.2423-3974T>C		intron_variant		5	NM_025074.7	ENSP00000422834	P1
FRAS1	ENST00000325942.11	c.2423-3974T>C		intron_variant		1		ENSP00000326330
FRAS1	ENST00000682513.1	c.2423-3974T>C		intron_variant				ENSP00000508201
FRAS1	ENST00000684159.1	c.2423-3974T>C		intron_variant				ENSP00000506875

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97751 AN: 151652 Hom.: 32107 Cov.: 30

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.645 AC: 97845 AN: 151772 Hom.: 32134 Cov.: 30 AF XY: 0.639 AC XY: 47379 AN XY: 74152

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.629

Alfa AF: 0.644 Hom.: 48714

Bravo AF: 0.644

Asia WGS AF: 0.371 AC: 1293 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.64

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: rs1268789; hg19: chr4-79280693;