Genetic Variant HEATR5B:c.3854-36A>G (chr2-37020872-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019024.3(HEATR5B):c.3854-36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,219,088 control chromosomes in the GnomAD database, including 27,457 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3306 hom., cov: 32)

Exomes 𝑓: 0.20 ( 24151 hom. )

Consequence

HEATR5B
NM_019024.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00700

Publications

25 publications found

Variant links:

Genes affected

HEATR5B (HGNC:29273): (HEAT repeat containing 5B) Predicted to be involved in endocytosis; protein localization; and retrograde transport, endosome to Golgi. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

HEATR5B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019024.3. 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
	HEATR5B	NM_019024.3	MANE Select	c.3854-36A>G		intron	N/A	NP_061897.1	Q9P2D3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HEATR5B	ENST00000233099.6	TSL:1 MANE Select	c.3854-36A>G	intron	N/A	ENSP00000233099.5	Q9P2D3-1
HEATR5B	ENST00000903982.1		c.3854-36A>G	intron	N/A	ENSP00000574041.1
HEATR5B	ENST00000920714.1		c.3854-36A>G	intron	N/A	ENSP00000590773.1

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28286

AN:

151954

Hom.:

3293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0877

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.242

AC:

27683

AN:

114490

AF XY:

0.243

show subpopulations

Gnomad AFR exome

AF:

0.0908

Gnomad AMR exome

AF:

0.336

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.200

AC:

213828

AN:

1067016

Hom.:

24151

Cov.:

AF XY:

0.202

AC XY:

106107

AN XY:

525638

show subpopulations

African (AFR)

AF:

0.0786

AC:

1778

AN:

22632

American (AMR)

AF:

0.294

AC:

5171

AN:

17612

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

2816

AN:

17572

East Asian (EAS)

AF:

0.553

AC:

16620

AN:

30028

South Asian (SAS)

AF:

0.283

AC:

12813

AN:

45246

European-Finnish (FIN)

AF:

0.222

AC:

10007

AN:

45038

Middle Eastern (MID)

AF:

0.191

AC:

869

AN:

4544

European-Non Finnish (NFE)

AF:

0.184

AC:

154405

AN:

840040

Other (OTH)

AF:

0.211

AC:

9349

AN:

44304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

7413

14826

22240

29653

37066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5744

11488

17232

22976

28720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.186

AC:

28323

AN:

152072

Hom.:

3306

Cov.:

AF XY:

0.193

AC XY:

14363

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.0878

AC:

3646

AN:

41526

American (AMR)

AF:

0.245

AC:

3746

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

569

AN:

3472

East Asian (EAS)

AF:

0.533

AC:

2749

AN:

5158

South Asian (SAS)

AF:

0.320

AC:

1542

AN:

4818

European-Finnish (FIN)

AF:

0.216

AC:

2277

AN:

10532

Middle Eastern (MID)

AF:

0.151

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.193

AC:

13118

AN:

67970

Other (OTH)

AF:

0.193

AC:

407

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1139

2278

3416

4555

5694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.198

Hom.:

3078

Bravo

AF:

0.184

Asia WGS

AF:

0.402

AC:

1392

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

(source)

DANN

Benign

0.65

PhyloP100

0.0070

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over