rs886059622

Variant names:

• chr4-78057588-C-A
• rs886059622
• NM_025074.7:c.-422C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-78057588-C-A
• chr4-78057588-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025074.7(FRAS1):​c.-422C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000343 in 29,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: FRAS1 NM_025074.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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]

ENSG00000307921 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRAS1	NM_025074.7	c.-422C>A		5_prime_UTR_variant	Exon 1 of 74	ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2	c.-422C>A		5_prime_UTR_variant	Exon 1 of 42		NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4	c.-422C>A		5_prime_UTR_variant	Exon 1 of 74	5	NM_025074.7	ENSP00000422834.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000343 AC: 1 AN: 29182 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14736

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 1276

American (AMR) AF: 0.00 AC: 0 AN: 942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1204

East Asian (EAS) AF: 0.00 AC: 0 AN: 2000

South Asian (SAS) AF: 0.00 AC: 0 AN: 450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 158

European-Non Finnish (NFE) AF: 0.0000510 AC: 1 AN: 19590

Other (OTH) AF: 0.00 AC: 0 AN: 2006

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		-0.011
PromoterAI		-0.050	Neutral

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: rs886059622; hg19: chr4-78978742;