4-78158603-C-T

Variant names:

• chr4-78158603-C-T
• rs17002988
• NM_025074.7:c.109-78907C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025074.7(FRAS1):​c.109-78907C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,004 control chromosomes in the GnomAD database, including 25,344 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 0.55 (25344 hom., cov: 31)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRAS1	NM_025074.7	MANE Select	c.109-78907C>T		intron	N/A	NP_079350.5
	FRAS1	NM_001166133.2		c.109-78907C>T		intron	N/A	NP_001159605.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRAS1	ENST00000512123.4	TSL:5 MANE Select	c.109-78907C>T		intron	N/A	ENSP00000422834.2
	FRAS1	ENST00000325942.11	TSL:1	c.109-78907C>T		intron	N/A	ENSP00000326330.6
	FRAS1	ENST00000508900.2	TSL:1	c.109-78907C>T		intron	N/A	ENSP00000423809.2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84132 AN: 151886 Hom.: 25348 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.554 AC: 84148 AN: 152004 Hom.: 25344 Cov.: 31 AF XY: 0.551 AC XY: 40915 AN XY: 74266

African (AFR) AF: 0.305 AC: 12640 AN: 41470

American (AMR) AF: 0.631 AC: 9641 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2345 AN: 3472

East Asian (EAS) AF: 0.518 AC: 2666 AN: 5146

South Asian (SAS) AF: 0.638 AC: 3076 AN: 4822

European-Finnish (FIN) AF: 0.585 AC: 6171 AN: 10542

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45753 AN: 67954

Other (OTH) AF: 0.587 AC: 1237 AN: 2108

Alfa AF: 0.621 Hom.: 57008

Bravo AF: 0.551

Asia WGS AF: 0.536 AC: 1865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.58
PhyloP100		0.045
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: rs17002988; hg19: chr4-79079757;