4-78306508-C-T

Variant names:

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

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>T 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 0.28 (2488 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=-1.01).

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>T		intron	N/A	NP_079350.5
	FRAS1	NM_001166133.2		c.1535-1558C>T		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>T		intron	N/A	ENSP00000422834.2	Q86XX4-2
	FRAS1	ENST00000325942.11	TSL:1	c.1535-1558C>T		intron	N/A	ENSP00000326330.6	Q86XX4-5
	FRAS1	ENST00000508900.2	TSL:1	c.1535-1558C>T		intron	N/A	ENSP00000423809.2	Q86XX4-6

Frequencies

GnomAD3 genomes AF: 0.276 AC: 12566 AN: 45590 Hom.: 2483 Cov.: 6

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0378

Gnomad SAS AF: 0.0581

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.246

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: AS_VQSR AF: 0.276 AC: 12583 AN: 45610 Hom.: 2488 Cov.: 6 AF XY: 0.256 AC XY: 5699 AN XY: 22220

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.443 AC: 4512 AN: 10182

American (AMR) AF: 0.224 AC: 1061 AN: 4734

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 210 AN: 1356

East Asian (EAS) AF: 0.0373 AC: 102 AN: 2736

South Asian (SAS) AF: 0.0588 AC: 137 AN: 2328

European-Finnish (FIN) AF: 0.228 AC: 583 AN: 2562

Middle Eastern (MID) AF: 0.221 AC: 30 AN: 136

European-Non Finnish (NFE) AF: 0.277 AC: 5692 AN: 20580

Other (OTH) AF: 0.241 AC: 167 AN: 692

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.588 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	1.6
DANN	Benign	0.63
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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;