Variant rs34402828 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004821.3(HAND1):c.468T>G(p.Ser156Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,614,134 control chromosomes in the GnomAD database, including 2,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 180 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2596 hom. )

Consequence

HAND1
NM_004821.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0570

Variant links:

Genes affected

HAND1 (HGNC:4807): (heart and neural crest derivatives expressed 1) The protein encoded by this gene belongs to the basic helix-loop-helix family of transcription factors. This gene product is one of two closely related family members, the HAND proteins, which are asymmetrically expressed in the developing ventricular chambers and play an essential role in cardiac morphogenesis. Working in a complementary fashion, they function in the formation of the right ventricle and aortic arch arteries, implicating them as mediators of congenital heart disease. In addition, it has been suggested that this transcription factor may be required for early trophoblast differentiation. [provided by RefSeq, Jul 2008]

HAND1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 5-154477541-A-C is Benign according to our data. Variant chr5-154477541-A-C is described in ClinVar as [Benign]. Clinvar id is 413856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-154477541-A-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.057 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAND1	NM_004821.3 linkuse as main transcript	c.468T>G	p.Ser156Ser	synonymous_variant	1/2	ENST00000231121.3	NP_004812.1
HAND1	XM_005268531.2 linkuse as main transcript	c.468T>G	p.Ser156Ser	synonymous_variant	1/2		XP_005268588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAND1	ENST00000231121.3 linkuse as main transcript	c.468T>G	p.Ser156Ser	synonymous_variant	1/2	1	NM_004821.3	ENSP00000231121.2		O96004

Frequencies

GnomAD3 genomes

AF:

0.0449

AC:

6829

AN:

152160

Hom.:

181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0523

Gnomad ASJ

AF:

0.0733

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0512

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0658

Gnomad OTH

AF:

0.0507

GnomAD3 exomes

AF:

0.0466

AC:

11721

AN:

251346

Hom.:

360

AF XY:

0.0473

AC XY:

6423

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0411

Gnomad ASJ exome

AF:

0.0837

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0190

Gnomad FIN exome

AF:

0.0493

Gnomad NFE exome

AF:

0.0638

Gnomad OTH exome

AF:

0.0612

GnomAD4 exome

AF:

0.0562

AC:

82192

AN:

1461856

Hom.:

2596

Cov.:

AF XY:

0.0555

AC XY:

40372

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00911

Gnomad4 AMR exome

AF:

0.0431

Gnomad4 ASJ exome

AF:

0.0784

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0184

Gnomad4 FIN exome

AF:

0.0481

Gnomad4 NFE exome

AF:

0.0631

Gnomad4 OTH exome

AF:

0.0548

GnomAD4 genome

AF:

0.0448

AC:

6827

AN:

152278

Hom.:

180

Cov.:

AF XY:

0.0437

AC XY:

3251

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.0522

Gnomad4 ASJ

AF:

0.0733

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.0512

Gnomad4 NFE

AF:

0.0658

Gnomad4 OTH

AF:

0.0501

Alfa

AF:

0.0516

Hom.:

157

Bravo

AF:

0.0431

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0704

EpiControl

AF:

0.0734

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jul 29, 2023

- -

Hypoplastic left heart syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.2

DANN

Benign

0.65

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

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