NM_025074.7:c.3151+14_3151+15dupTG

Variant names:

• chr4-78374264-C-CTG
• rs398092530
• NM_025074.7:c.3151+14_3151+15dupTG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_025074.7(FRAS1):​c.3151+14_3151+15dupTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,561,108 control chromosomes in the GnomAD database, including 103,737 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11138 hom., cov: 0)
  • Exomes 𝑓: 0.36 (92599 hom.)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.47
• Publications: 2 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 -16 ACMG points.

• BP6: Variant 4-78374264-C-CTG is Benign according to our data. Variant chr4-78374264-C-CTG is described in ClinVar as Benign. ClinVar VariationId is 261806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 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.3151+14_3151+15dupTG		intron	N/A	NP_079350.5
	FRAS1	NM_001166133.2		c.3151+14_3151+15dupTG		intron	N/A	NP_001159605.1	Q86XX4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRAS1	ENST00000512123.4	TSL:5 MANE Select	c.3151+13_3151+14insTG		intron	N/A	ENSP00000422834.2	Q86XX4-2
	FRAS1	ENST00000325942.11	TSL:1	c.3151+13_3151+14insTG		intron	N/A	ENSP00000326330.6	Q86XX4-5
	FRAS1	ENST00000915768.1		c.3151+13_3151+14insTG		intron	N/A	ENSP00000585827.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57478 AN: 151822 Hom.: 11129 Cov.: 0

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.337 AC: 82353 AN: 244358 AF XY: 0.331

Gnomad AFR exome AF: 0.467

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.307

Gnomad EAS exome AF: 0.342

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.343

GnomAD4 exome AF: 0.359 AC: 505254 AN: 1409168 Hom.: 92599 Cov.: 30 AF XY: 0.354 AC XY: 245645 AN XY: 694690

African (AFR) AF: 0.468 AC: 15318 AN: 32706

American (AMR) AF: 0.309 AC: 13512 AN: 43752

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 7509 AN: 25072

East Asian (EAS) AF: 0.343 AC: 13234 AN: 38626

South Asian (SAS) AF: 0.230 AC: 18526 AN: 80442

European-Finnish (FIN) AF: 0.315 AC: 16354 AN: 51892

Middle Eastern (MID) AF: 0.351 AC: 1905 AN: 5434

European-Non Finnish (NFE) AF: 0.371 AC: 398390 AN: 1073596

Other (OTH) AF: 0.356 AC: 20506 AN: 57648

GnomAD4 genome AF: 0.379 AC: 57529 AN: 151940 Hom.: 11138 Cov.: 0 AF XY: 0.373 AC XY: 27730 AN XY: 74294

African (AFR) AF: 0.468 AC: 19349 AN: 41376

American (AMR) AF: 0.344 AC: 5261 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3470

East Asian (EAS) AF: 0.340 AC: 1758 AN: 5164

South Asian (SAS) AF: 0.224 AC: 1079 AN: 4814

European-Finnish (FIN) AF: 0.312 AC: 3291 AN: 10564

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24632 AN: 67960

Other (OTH) AF: 0.369 AC: 779 AN: 2112

Alfa AF: 0.363 Hom.: 1832

Bravo AF: 0.386

Asia WGS AF: 0.291 AC: 1010 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Fraser syndrome 1 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs398092530; hg19: chr4-79295418;