rs10017687

Variant names:

• chr4-107989740-G-A
• rs10017687
• ENST00000505878:c.-16G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-107989740-G-A
• chr4-107989740-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000505878(HADH):​c.-16G>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 0.0069 in 604,978 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (102 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (17 hom.)
• Consequence: HADH ENST00000505878 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0240

Genes affected

HADH (HGNC:4799): (hydroxyacyl-CoA dehydrogenase) This gene is a member of the 3-hydroxyacyl-CoA dehydrogenase gene family. The encoded protein functions in the mitochondrial matrix to catalyze the oxidation of straight-chain 3-hydroxyacyl-CoAs as part of the beta-oxidation pathway. Its enzymatic activity is highest with medium-chain-length fatty acids. Mutations in this gene cause one form of familial hyperinsulinemic hypoglycemia. The human genome contains a related pseudogene of this gene on chromosome 15. [provided by RefSeq, May 2010]

CYP2U1-AS1 (HGNC:54817): (CYP2U1 and SGMS2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-107989740-G-A is Benign according to our data. Variant chr4-107989740-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 347123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HADH	ENST00000505878	c.-16G>A		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000425952.2
HADH	ENST00000603302	c.-193G>A		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000474560.1
CYP2U1-AS1	ENST00000658105.3	n.-16C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3046 AN: 152178 Hom.: 101 Cov.: 33

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00987

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00677

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0138

GnomAD3 exomes AF: 0.00431 AC: 137 AN: 31786 Hom.: 2 AF XY: 0.00361 AC XY: 59 AN XY: 16366

Gnomad AFR exome AF: 0.0656

Gnomad AMR exome AF: 0.00433

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00563

Gnomad SAS exome AF: 0.000883

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000451

Gnomad OTH exome AF: 0.000847

GnomAD4 exome AF: 0.00248 AC: 1124 AN: 452682 Hom.: 17 Cov.: 5 AF XY: 0.00215 AC XY: 514 AN XY: 238954

Gnomad4 AFR exome AF: 0.0623

Gnomad4 AMR exome AF: 0.00525

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00595

Gnomad4 SAS exome AF: 0.000475

Gnomad4 FIN exome AF: 0.0000338

Gnomad4 NFE exome AF: 0.000344

Gnomad4 OTH exome AF: 0.00629

GnomAD4 genome AF: 0.0200 AC: 3049 AN: 152296 Hom.: 102 Cov.: 33 AF XY: 0.0193 AC XY: 1434 AN XY: 74470

Gnomad4 AFR AF: 0.0676

Gnomad4 AMR AF: 0.00986

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00679

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0173 Hom.: 9

Bravo AF: 0.0235

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Deficiency of 3-hydroxyacyl-CoA dehydrogenase Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hyperinsulinemic hypoglycemia, familial, 4 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10017687; hg19: chr4-108910896;