chr4-78156244-G-C

Variant names:

• chr4-78156244-G-C
• rs6838661
• NM_025074.7:c.109-81266G>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.109-81266G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,066 control chromosomes in the GnomAD database, including 2,060 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 0.16 (2060 hom., cov: 32)
• Consequence: FRAS1 NM_025074.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7	c.109-81266G>C		intron_variant	Intron 2 of 73	ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2	c.109-81266G>C		intron_variant	Intron 2 of 41		NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4	c.109-81266G>C		intron_variant	Intron 2 of 73	5	NM_025074.7	ENSP00000422834.2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23863 AN: 151954 Hom.: 2062 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.157 AC: 23863 AN: 152066 Hom.: 2060 Cov.: 32 AF XY: 0.154 AC XY: 11478 AN XY: 74318

African (AFR) AF: 0.110 AC: 4549 AN: 41490

American (AMR) AF: 0.152 AC: 2320 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3468

East Asian (EAS) AF: 0.0529 AC: 274 AN: 5180

South Asian (SAS) AF: 0.0714 AC: 344 AN: 4818

European-Finnish (FIN) AF: 0.218 AC: 2290 AN: 10516

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13051 AN: 67998

Other (OTH) AF: 0.151 AC: 319 AN: 2110

Alfa AF: 0.172 Hom.: 292

Bravo AF: 0.150

Asia WGS AF: 0.0740 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.66
PhyloP100		1.2
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

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Other links and lift over

dbSNP: rs6838661; hg19: chr4-79077398;