rs34198899

Variant summary

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

The NM_004821.3(HAND1):c.531G>C(p.Arg177=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 1,613,830 control chromosomes in the GnomAD database, including 2,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 214 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2539 hom. )

Consequence

HAND1
NM_004821.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.17

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=-0.49).

BP6

Variant 5-154477478-C-G is Benign according to our data. Variant chr5-154477478-C-G is described in ClinVar as [Benign]. Clinvar id is 413857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAND1	NM_004821.3 linkuse as main transcript	c.531G>C	p.Arg177=	synonymous_variant	1/2	ENST00000231121.3
HAND1	XM_005268531.2 linkuse as main transcript	c.531G>C	p.Arg177=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAND1	ENST00000231121.3 linkuse as main transcript	c.531G>C	p.Arg177=	synonymous_variant	1/2	1	NM_004821.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0435

AC:

6622

AN:

152168

Hom.:

214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0499

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.0907

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0601

Gnomad OTH

AF:

0.0430

GnomAD3 exomes

AF:

0.0465

AC:

11617

AN:

249954

Hom.:

373

AF XY:

0.0471

AC XY:

6362

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.00918

Gnomad AMR exome

AF:

0.0511

Gnomad ASJ exome

AF:

0.0198

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0318

Gnomad FIN exome

AF:

0.0831

Gnomad NFE exome

AF:

0.0574

Gnomad OTH exome

AF:

0.0466

GnomAD4 exome

AF:

0.0559

AC:

81742

AN:

1461544

Hom.:

2539

Cov.:

AF XY:

0.0554

AC XY:

40251

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00807

Gnomad4 AMR exome

AF:

0.0529

Gnomad4 ASJ exome

AF:

0.0222

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.0331

Gnomad4 FIN exome

AF:

0.0790

Gnomad4 NFE exome

AF:

0.0617

Gnomad4 OTH exome

AF:

0.0457

GnomAD4 genome

AF:

0.0435

AC:

6620

AN:

152286

Hom.:

214

Cov.:

AF XY:

0.0446

AC XY:

3325

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.0500

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.0907

Gnomad4 NFE

AF:

0.0601

Gnomad4 OTH

AF:

0.0426

Alfa

AF:

0.0513

Hom.:

Bravo

AF:

0.0386

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0517

EpiControl

AF:

0.0539

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

Oct 09, 2023

- -

HAND1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hypoplastic left heart syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Benign

0.79

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