Variant 14-73498212-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001220484.1(HEATR4):c.2489G>A(p.Arg830Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

HEATR4
NM_001220484.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.751

Variant links:

Genes affected

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

HEATR4 links:

ACOT1 (HGNC:33128): (acyl-CoA thioesterase 1) Enables acyl-CoA hydrolase activity. Involved in acyl-CoA metabolic process; long-chain fatty acid metabolic process; and very long-chain fatty acid metabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACOT1 links:

HEATR4 (HGNC:):

HEATR4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019074142).

BP6

Variant 14-73498212-C-T is Benign according to our data. Variant chr14-73498212-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3104801.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEATR4	NM_001220484.1 linkuse as main transcript	c.2489G>A	p.Arg830Gln	missense_variant	14/18	ENST00000553558.6	NP_001207413.1	Q86WZ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEATR4	ENST00000553558.6 linkuse as main transcript	c.2489G>A	p.Arg830Gln	missense_variant	14/18	2	NM_001220484.1	ENSP00000450444.2		Q86WZ0
HEATR4	ENST00000334988.2 linkuse as main transcript	c.2489G>A	p.Arg830Gln	missense_variant	13/17	1		ENSP00000335447.2		Q86WZ0

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000151

AC:

AN:

251418

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000752

AC:

110

AN:

1461830

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.4

DANN

Benign

0.93

DEOGEN2

Benign

0.098

T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.57

.;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.36

N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.064

Sift

Benign

0.20

T;T

Sift4G

Uncertain

0.034

D;D

Polyphen

0.056

B;B

Vest4

0.21

MVP

0.17

MPC

0.13

ClinPred

0.019

GERP RS

-1.4

Varity_R

0.033

gMVP

0.080

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over