4-78470102-T-C

Variant names:

• chr4-78470102-T-C
• rs7664505
• NM_025074.7:c.7371+11T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_025074.7(FRAS1):​c.7371+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,580,422 control chromosomes in the GnomAD database, including 777,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70583 hom., cov: 31)
  • Exomes 𝑓: 0.99 (706709 hom.)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.69
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-78470102-T-C is Benign according to our data. Variant chr4-78470102-T-C is described in ClinVar as Benign. ClinVar VariationId is 261814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 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.7371+11T>C		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.7371+11T>C		intron	N/A	ENSP00000422834.2	Q86XX4-2
	FRAS1	ENST00000915768.1		c.7143+11T>C		intron	N/A	ENSP00000585827.1
	FRAS1	ENST00000682513.1		c.7371+11T>C		intron	N/A	ENSP00000508201.1	A0A804HL50

Frequencies

GnomAD3 genomes AF: 0.962 AC: 146270 AN: 152116 Hom.: 70531 Cov.: 31

Gnomad AFR AF: 0.871

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.974

GnomAD2 exomes AF: 0.988 AC: 239608 AN: 242414 AF XY: 0.991

Gnomad AFR exome AF: 0.862

Gnomad AMR exome AF: 0.989

Gnomad ASJ exome AF: 0.988

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.998

Gnomad OTH exome AF: 0.993

GnomAD4 exome AF: 0.995 AC: 1420475 AN: 1428188 Hom.: 706709 Cov.: 23 AF XY: 0.995 AC XY: 708644 AN XY: 712026

African (AFR) AF: 0.863 AC: 28298 AN: 32794

American (AMR) AF: 0.987 AC: 43636 AN: 44204

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 25500 AN: 25788

East Asian (EAS) AF: 1.00 AC: 39249 AN: 39250

South Asian (SAS) AF: 0.999 AC: 84453 AN: 84506

European-Finnish (FIN) AF: 1.00 AC: 53173 AN: 53174

Middle Eastern (MID) AF: 0.986 AC: 5617 AN: 5694

European-Non Finnish (NFE) AF: 0.999 AC: 1082013 AN: 1083516

Other (OTH) AF: 0.988 AC: 58536 AN: 59262

GnomAD4 genome AF: 0.962 AC: 146381 AN: 152234 Hom.: 70583 Cov.: 31 AF XY: 0.963 AC XY: 71629 AN XY: 74418

African (AFR) AF: 0.871 AC: 36145 AN: 41502

American (AMR) AF: 0.982 AC: 15032 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 3442 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5180

South Asian (SAS) AF: 1.00 AC: 4813 AN: 4814

European-Finnish (FIN) AF: 1.00 AC: 10608 AN: 10610

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67909 AN: 68036

Other (OTH) AF: 0.974 AC: 2057 AN: 2112

Alfa AF: 0.969 Hom.: 21819

Bravo AF: 0.955

Asia WGS AF: 0.990 AC: 3442 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Fraser syndrome 1 (3)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.072
DANN	Benign	0.33
PhyloP100		-1.7
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: rs7664505; hg19: chr4-79391256;