Genetic Variant NM_020733.2:c.4044G>A (chr3-124970754-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020733.2(HEG1):c.4044G>A(p.Pro1348Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,610,542 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

HEG1
NM_020733.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06

Publications

1 publications found

Variant links:

Genes affected

HEG1 (HGNC:29227): (heart development protein with EGF like domains 1) Predicted to enable calcium ion binding activity. Involved in several processes, including negative regulation of Rho protein signal transduction; negative regulation of Rho-dependent protein serine/threonine kinase activity; and negative regulation of membrane permeability. Located in cell-cell junction. [provided by Alliance of Genome Resources, Apr 2022]

HEG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 3-124970754-C-T is Benign according to our data. Variant chr3-124970754-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2654089.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.06 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020733.2. 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
	HEG1	NM_020733.2	MANE Select	c.4044G>A	p.Pro1348Pro	synonymous	Exon 17 of 17	NP_065784.1	Q9ULI3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEG1	ENST00000311127.9	TSL:5 MANE Select	c.4044G>A	p.Pro1348Pro	synonymous	Exon 17 of 17	ENSP00000311502.3	Q9ULI3-1
HEG1	ENST00000650592.2		c.4344G>A	p.Pro1448Pro	synonymous	Exon 18 of 18	ENSP00000515478.1	A0A994J6K3
HEG1	ENST00000480667.1	TSL:4	n.211G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

220

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.0903

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00111

AC:

270

AN:

242662

AF XY:

0.00115

show subpopulations

Gnomad AFR exome

AF:

0.000471

Gnomad AMR exome

AF:

0.000236

Gnomad ASJ exome

AF:

0.00193

Gnomad EAS exome

AF:

0.000114

Gnomad FIN exome

AF:

0.000800

Gnomad NFE exome

AF:

0.00176

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.00159

AC:

2326

AN:

1458368

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1151

AN XY:

725000

show subpopulations

African (AFR)

AF:

0.000389

AC:

AN:

33450

American (AMR)

AF:

0.000203

AC:

AN:

44276

Ashkenazi Jewish (ASJ)

AF:

0.00281

AC:

AN:

26012

East Asian (EAS)

AF:

0.000151

AC:

AN:

39636

South Asian (SAS)

AF:

0.000611

AC:

AN:

85172

European-Finnish (FIN)

AF:

0.000751

AC:

AN:

53238

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00185

AC:

2058

AN:

1110534

Other (OTH)

AF:

0.00123

AC:

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

110

221

331

442

552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.00145

AC:

220

AN:

152174

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.000458

AC:

AN:

41502

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000416

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00149

AC:

101

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00166

Hom.:

Bravo

AF:

0.00197

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.2

(source)

DANN

Benign

0.70

PhyloP100

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(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