1-154983399-TGA-T

Variant names:

• chr1-154983399-TGA-T
• rs569007120
• NM_025207.5:c.-292_-291delAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_025207.5(FLAD1):​c.-292_-291delAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 286,006 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0047 (4 hom.)
• Consequence: FLAD1 NM_025207.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

Genes affected

FLAD1 (HGNC:24671): (flavin adenine dinucleotide synthetase 1) This gene encodes the enzyme that catalyzes adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

FLAD1 Gene-Disease associations (from GenCC):

• myopathy with abnormal lipid metabolism

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-154983399-TGA-T is Benign according to our data. Variant chr1-154983399-TGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 419775.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00373 (567/151872) while in subpopulation SAS AF = 0.0169 (81/4796). AF 95% confidence interval is 0.0139. There are 2 homozygotes in GnomAd4. There are 284 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLAD1	NM_025207.5	c.-292_-291delAG		5_prime_UTR_variant	Exon 1 of 7	ENST00000292180.8	NP_079483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLAD1	ENST00000292180.8	c.-292_-291delAG		5_prime_UTR_variant	Exon 1 of 7	1	NM_025207.5	ENSP00000292180.3

Frequencies

GnomAD3 genomes AF: 0.00374 AC: 568 AN: 151758 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000775

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.0169

Gnomad FIN AF: 0.000757

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00487

Gnomad OTH AF: 0.00336

GnomAD4 exome AF: 0.00473 AC: 635 AN: 134134 Hom.: 4 AF XY: 0.00479 AC XY: 329 AN XY: 68750

African (AFR) AF: 0.000626 AC: 3 AN: 4794

American (AMR) AF: 0.00161 AC: 9 AN: 5578

Ashkenazi Jewish (ASJ) AF: 0.00800 AC: 43 AN: 5376

East Asian (EAS) AF: 0.000265 AC: 3 AN: 11324

South Asian (SAS) AF: 0.0145 AC: 74 AN: 5096

European-Finnish (FIN) AF: 0.000529 AC: 4 AN: 7562

Middle Eastern (MID) AF: 0.0129 AC: 9 AN: 700

European-Non Finnish (NFE) AF: 0.00521 AC: 443 AN: 84958

Other (OTH) AF: 0.00537 AC: 47 AN: 8746

GnomAD4 genome AF: 0.00373 AC: 567 AN: 151872 Hom.: 2 Cov.: 31 AF XY: 0.00383 AC XY: 284 AN XY: 74192

African (AFR) AF: 0.000748 AC: 31 AN: 41436

American (AMR) AF: 0.00301 AC: 46 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3466

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5142

South Asian (SAS) AF: 0.0169 AC: 81 AN: 4796

European-Finnish (FIN) AF: 0.000757 AC: 8 AN: 10570

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00488 AC: 331 AN: 67892

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00362 Hom.: 2

Bravo AF: 0.00362

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 01, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
Mutation Taster		=73/27	polymorphism

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: rs569007120; hg19: chr1-154955875;