rs10518200

chr4-78519593-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 4-78519593-A-T is Benign according to our data. Variant chr4-78519593-A-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRAS1	NM_025074.7	c.10540+112A>T		intron_variant		ENST00000512123.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRAS1	ENST00000512123.4	c.10540+112A>T		intron_variant		5	NM_025074.7	P1

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

Gnomad4 AFR exome AF: 0.0749

Gnomad4 AMR exome AF: 0.0869

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.00198

Gnomad4 SAS exome AF: 0.0578

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.159

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

Gnomad4 AFR AF: 0.0777

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0529

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.132

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.18
Dann	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs10518200; hg19: chr4-79440747;