rs144640661

Variant names:

• chr19-51347050-G-A
• rs144640661
• NM_001985.3:c.447C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001985.3(ETFB):​c.447C>T​(p.Phe149Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,613,998 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (59 hom.)
• Consequence: ETFB NM_001985.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0760
• Publications: 3 publications found

Genes affected

ETFB (HGNC:3482): (electron transfer flavoprotein subunit beta) This gene encodes electron-transfer-flavoprotein, beta polypeptide, which shuttles electrons between primary flavoprotein dehydrogenases involved in mitochondrial fatty acid and amino acid catabolism and the membrane-bound electron transfer flavoprotein ubiquinone oxidoreductase. The gene deficiencies have been implicated in type II glutaricaciduria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

ETFB Gene-Disease associations (from GenCC):

• multiple acyl-CoA dehydrogenase deficiency

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

ENSG00000267984 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 19-51347050-G-A is Benign according to our data. Variant chr19-51347050-G-A is described in ClinVar as Benign. ClinVar VariationId is 203698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.076 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0042 (639/152306) while in subpopulation EAS AF = 0.04 (207/5174). AF 95% confidence interval is 0.0355. There are 6 homozygotes in GnomAd4. There are 369 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001985.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETFB	NM_001985.3	MANE Select	c.447C>T	p.Phe149Phe	synonymous	Exon 5 of 6	NP_001976.1	P38117-1
	ETFB	NM_001014763.1		c.720C>T	p.Phe240Phe	synonymous	Exon 4 of 5	NP_001014763.1	P38117-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETFB	ENST00000309244.9	TSL:1 MANE Select	c.447C>T	p.Phe149Phe	synonymous	Exon 5 of 6	ENSP00000311930.3	P38117-1
	ETFB	ENST00000354232.8	TSL:1	c.720C>T	p.Phe240Phe	synonymous	Exon 4 of 5	ENSP00000346173.3	P38117-2
	ETFB	ENST00000903309.1		c.522C>T	p.Phe174Phe	synonymous	Exon 6 of 7	ENSP00000573368.1

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 640 AN: 152188 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00769 AC: 1926 AN: 250364 AF XY: 0.00768

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.0437

Gnomad FIN exome AF: 0.00587

Gnomad NFE exome AF: 0.000645

Gnomad OTH exome AF: 0.00474

GnomAD4 exome AF: 0.00307 AC: 4486 AN: 1461692 Hom.: 59 Cov.: 34 AF XY: 0.00328 AC XY: 2384 AN XY: 727128

African (AFR) AF: 0.00161 AC: 54 AN: 33480

American (AMR) AF: 0.0131 AC: 587 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26132

East Asian (EAS) AF: 0.0434 AC: 1721 AN: 39694

South Asian (SAS) AF: 0.0117 AC: 1006 AN: 86222

European-Finnish (FIN) AF: 0.00478 AC: 255 AN: 53358

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.000488 AC: 543 AN: 1111948

Other (OTH) AF: 0.00513 AC: 310 AN: 60388

GnomAD4 genome AF: 0.00420 AC: 639 AN: 152306 Hom.: 6 Cov.: 32 AF XY: 0.00496 AC XY: 369 AN XY: 74462

African (AFR) AF: 0.00180 AC: 75 AN: 41562

American (AMR) AF: 0.0131 AC: 201 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0400 AC: 207 AN: 5174

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4832

European-Finnish (FIN) AF: 0.00499 AC: 53 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68028

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00107 Hom.: 0

Bravo AF: 0.00516

Asia WGS AF: 0.0240 AC: 83 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Multiple acyl-CoA dehydrogenase deficiency (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		0.076
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs144640661; hg19: chr19-51850304; COSMIC: COSV58535436; COSMIC: COSV58535436;