4-78057777-A-G

Variant names:

• chr4-78057777-A-G
• rs566584457
• NM_025074.7:c.-233A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025074.7(FRAS1):​c.-233A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FRAS1 NM_025074.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Fraser syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Fraser syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• renal agenesis, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7	c.-233A>G		5_prime_UTR_variant	Exon 1 of 74	ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2	c.-233A>G		5_prime_UTR_variant	Exon 1 of 42		NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4	c.-233A>G		5_prime_UTR_variant	Exon 1 of 74	5	NM_025074.7	ENSP00000422834.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 399798 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 207124

African (AFR) AF: 0.00 AC: 0 AN: 11404

American (AMR) AF: 0.00 AC: 0 AN: 17188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12538

East Asian (EAS) AF: 0.00 AC: 0 AN: 29338

South Asian (SAS) AF: 0.00 AC: 0 AN: 32452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1790

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 242716

Other (OTH) AF: 0.00 AC: 0 AN: 23988

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		0.24
PromoterAI		0.084	Neutral
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

Other links and lift over

dbSNP: rs566584457; hg19: chr4-78978931;