4-78065360-A-T

Position:

• chr4-78065360-A-T

Variant summary

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

The NM_025074.7(FRAS1):​c.77-625A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,212 control chromosomes in the GnomAD database, including 4,969 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 0.25 (4969 hom., cov: 30)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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]

FRAS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRAS1	NM_025074.7	c.77-625A>T		intron_variant		ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2	c.77-625A>T		intron_variant			NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4	c.77-625A>T		intron_variant		5	NM_025074.7	ENSP00000422834.2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37208 AN: 151108 Hom.: 4958 Cov.: 30

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.246 AC: 37243 AN: 151212 Hom.: 4969 Cov.: 30 AF XY: 0.251 AC XY: 18536 AN XY: 73820

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.261

Alfa AF: 0.226 Hom.: 505

Bravo AF: 0.252

Asia WGS AF: 0.277 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.41

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: rs1502885; hg19: chr4-78986514;