1-154983399-TGA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000315144.14(FLAD1):c.-145+6_-145+7del variant causes a splice donor region, intron 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 ENST00000315144.14 splice_donor_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.86

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]

ACMG classification

Verdict is Benign. Variant got -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. Variant chr1-154983399-TGA-T is described in Lovd as [Likely_benign].
• 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLAD1	NM_025207.5	c.-292_-291del		5_prime_UTR_variant	1/7	ENST00000292180.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLAD1	ENST00000292180.8	c.-292_-291del		5_prime_UTR_variant	1/7	1	NM_025207.5

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

Gnomad4 AFR exome AF: 0.000626

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00800

Gnomad4 EAS exome AF: 0.000265

Gnomad4 SAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.000529

Gnomad4 NFE exome AF: 0.00521

Gnomad4 OTH exome AF: 0.00537

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

Gnomad4 AFR AF: 0.000748

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.0169

Gnomad4 FIN AF: 0.000757

Gnomad4 NFE AF: 0.00488

Gnomad4 OTH AF: 0.00332

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

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 01, 2018

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

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: rs569007120; hg19: chr1-154955875;