rs10518200

Variant names:

• chr4-78519593-A-T
• rs10518200
• NM_025074.7:c.10540+112A>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.10540+112A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,264,390 control chromosomes in the GnomAD database, including 22,088 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 0.14 (1782 hom., cov: 31)
  • Exomes 𝑓: 0.18 (20306 hom.)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRAS1	NM_025074.7	MANE Select	c.10540+112A>T		intron	N/A	NP_079350.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRAS1	ENST00000512123.4	TSL:5 MANE Select	c.10540+112A>T		intron	N/A	ENSP00000422834.2	Q86XX4-2
	FRAS1	ENST00000915768.1		c.10312+112A>T		intron	N/A	ENSP00000585827.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21223 AN: 152080 Hom.: 1782 Cov.: 31

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0530

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.180 AC: 199938 AN: 1112192 Hom.: 20306 AF XY: 0.176 AC XY: 99338 AN XY: 565028

African (AFR) AF: 0.0749 AC: 1832 AN: 24462

American (AMR) AF: 0.0869 AC: 2541 AN: 29234

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2418 AN: 21574

East Asian (EAS) AF: 0.00198 AC: 72 AN: 36390

South Asian (SAS) AF: 0.0578 AC: 4022 AN: 69630

European-Finnish (FIN) AF: 0.156 AC: 6110 AN: 39214

Middle Eastern (MID) AF: 0.0941 AC: 447 AN: 4748

European-Non Finnish (NFE) AF: 0.208 AC: 174804 AN: 838512

Other (OTH) AF: 0.159 AC: 7692 AN: 48428

GnomAD4 genome AF: 0.139 AC: 21223 AN: 152198 Hom.: 1782 Cov.: 31 AF XY: 0.134 AC XY: 10000 AN XY: 74410

African (AFR) AF: 0.0777 AC: 3230 AN: 41548

American (AMR) AF: 0.116 AC: 1773 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3470

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5186

South Asian (SAS) AF: 0.0529 AC: 255 AN: 4824

European-Finnish (FIN) AF: 0.147 AC: 1559 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13581 AN: 67978

Other (OTH) AF: 0.132 AC: 279 AN: 2106

Alfa AF: 0.160 Hom.: 269

Bravo AF: 0.135

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.45
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10518200; hg19: chr4-79440747;