1-154983391-C-T

Variant names:

• chr1-154983391-C-T
• rs537748007
• NM_025207.5:c.-304C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_025207.5(FLAD1):​c.-304C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000811 in 270,066 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00087 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00073 (3 hom.)
• Consequence: FLAD1 NM_025207.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.166
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-154983391-C-T is Benign according to our data. Variant chr1-154983391-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 389482.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000874 (133/152214) while in subpopulation SAS AF = 0.0272 (131/4820). AF 95% confidence interval is 0.0234. There are 1 homozygotes in GnomAd4. There are 101 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLAD1	NM_025207.5	c.-304C>T		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.-304C>T		5_prime_UTR_variant	Exon 1 of 7	1	NM_025207.5	ENSP00000292180.3

Frequencies

GnomAD3 genomes AF: 0.000888 AC: 135 AN: 152096 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000730 AC: 86 AN: 117852 Hom.: 3 Cov.: 0 AF XY: 0.00101 AC XY: 61 AN XY: 60294

African (AFR) AF: 0.00 AC: 0 AN: 4184

American (AMR) AF: 0.00 AC: 0 AN: 5026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4798

East Asian (EAS) AF: 0.00 AC: 0 AN: 9744

South Asian (SAS) AF: 0.0182 AC: 83 AN: 4560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 614

European-Non Finnish (NFE) AF: 0.0000267 AC: 2 AN: 74912

Other (OTH) AF: 0.000130 AC: 1 AN: 7684

GnomAD4 genome AF: 0.000874 AC: 133 AN: 152214 Hom.: 1 Cov.: 31 AF XY: 0.00136 AC XY: 101 AN XY: 74430

African (AFR) AF: 0.00 AC: 0 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0272 AC: 131 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67990

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000208 Hom.: 0

Bravo AF: 0.000125

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 02, 2017

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.4
DANN	Benign	0.75
PhyloP100		-0.17
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs537748007; hg19: chr1-154955867;