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rs34402828

chr5-154477541-A-Cchr5-154477541-A-G

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.Ser156=) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. S156S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.045 ( 180 hom., cov: 33)
Exomes 𝑓: 0.056 ( 2596 hom. )

Consequence

HAND1
NM_004821.3 synonymous

Scores

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.057 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
HAND1NM_004821.3 linkuse as main transcriptc.468T>G p.Ser156= synonymous_variant 1/2 ENST00000231121.3
HAND1XM_005268531.2 linkuse as main transcriptc.468T>G p.Ser156= synonymous_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HAND1ENST00000231121.3 linkuse as main transcriptc.468T>G p.Ser156= synonymous_variant 1/21 NM_004821.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0449
AC:
6829
AN:
152160
Hom.:
181
Cov.:
33
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.:
34
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0448
AC:
6827
AN:
152278
Hom.:
180
Cov.:
33
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:
32
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 submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpJul 29, 2023- -
Hypoplastic left heart syndrome Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 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.

Other links and lift over

dbSNP: rs34402828; hg19: chr5-153857101; API