dbSNP rs10518200: FRAS1:c.10540+112A>T (chr4-78519593-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.74

Publications

3 publications found

Variant links:

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

FRAS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7 link	c.10540+112A>T		intron_variant	Intron 67 of 73	ENST00000512123.4	NP_079350.5	Q86XX4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4 link	c.10540+112A>T		intron_variant	Intron 67 of 73	5	NM_025074.7	ENSP00000422834.2		Q86XX4-2

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21223

AN:

152080

Hom.:

1782

Cov.:

show subpopulations

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

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7739

15478

23217

30956

38695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5366

10732

16098

21464

26830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.139

AC:

21223

AN:

152198

Hom.:

1782

Cov.:

AF XY:

0.134

AC XY:

10000

AN XY:

74410

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.200

AC:

13581

AN:

67978

Other (OTH)

AF:

0.132

AC:

279

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

911

1823

2734

3646

4557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.45

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over