chr4-78313433-G-C

Variant names:

• chr4-78313433-G-C
• rs2061063
• NM_025074.7:c.1679-2161G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025074.7(FRAS1):​c.1679-2161G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,204 control chromosomes in the GnomAD database, including 5,507 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 0.26 (5507 hom., cov: 31)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7	c.1679-2161G>C		intron_variant	Intron 15 of 73	ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2	c.1679-2161G>C		intron_variant	Intron 15 of 41		NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4	c.1679-2161G>C		intron_variant	Intron 15 of 73	5	NM_025074.7	ENSP00000422834.2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38652 AN: 151086 Hom.: 5508 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0796

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.256 AC: 38654 AN: 151204 Hom.: 5507 Cov.: 31 AF XY: 0.249 AC XY: 18429 AN XY: 73902

African (AFR) AF: 0.148 AC: 6131 AN: 41290

American (AMR) AF: 0.236 AC: 3602 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 678 AN: 3454

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5164

South Asian (SAS) AF: 0.0794 AC: 380 AN: 4784

European-Finnish (FIN) AF: 0.335 AC: 3517 AN: 10506

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23432 AN: 67472

Other (OTH) AF: 0.258 AC: 542 AN: 2102

Alfa AF: 0.316 Hom.: 916

Bravo AF: 0.246

Asia WGS AF: 0.0530 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.68
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

Publications

LitVar

Other links and lift over

dbSNP: rs2061063; hg19: chr4-79234587;