chr4-78306508-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7	c.1535-1558C>T		intron_variant	Intron 14 of 73	ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2	c.1535-1558C>T		intron_variant	Intron 14 of 41		NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4	c.1535-1558C>T		intron_variant	Intron 14 of 73	5	NM_025074.7	ENSP00000422834.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 12566 AN: 45590 Hom.: 2483 Cov.: 6 FAILED QC

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

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0373

Gnomad4 SAS AF: 0.0588

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.241

Alfa AF: 0.588 Hom.: 1999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.63

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: rs345534; hg19: chr4-79227662;