chr4-78306508-C-A

Variant names:

• chr4-78306508-C-A
• rs345534
• NM_025074.7:c.1535-1558C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025074.7(FRAS1):​c.1535-1558C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 6)
  • Failed GnomAD Quality Control
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025074.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRAS1	NM_025074.7	MANE Select	c.1535-1558C>A		intron	N/A	NP_079350.5
	FRAS1	NM_001166133.2		c.1535-1558C>A		intron	N/A	NP_001159605.1	Q86XX4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRAS1	ENST00000512123.4	TSL:5 MANE Select	c.1535-1558C>A		intron	N/A	ENSP00000422834.2	Q86XX4-2
	FRAS1	ENST00000325942.11	TSL:1	c.1535-1558C>A		intron	N/A	ENSP00000326330.6	Q86XX4-5
	FRAS1	ENST00000508900.2	TSL:1	c.1535-1558C>A		intron	N/A	ENSP00000423809.2	Q86XX4-6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 52382 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 52382 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 25294

African (AFR) AF: 0.00 AC: 0 AN: 12032

American (AMR) AF: 0.00 AC: 0 AN: 5330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1540

East Asian (EAS) AF: 0.00 AC: 0 AN: 2900

South Asian (SAS) AF: 0.00 AC: 0 AN: 2448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 164

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 23952

Other (OTH) AF: 0.00 AC: 0 AN: 758

Alfa AF: 0.00 Hom.: 1999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.56
PhyloP100		-2.1

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: rs345534; hg19: chr4-79227662;