5-154477396-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004821.3(HAND1):c.543+70A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,217,788 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (58 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (41 hom.)
• Consequence: HAND1 NM_004821.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.179

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-154477396-T-C is Benign according to our data. Variant chr5-154477396-T-C is described in ClinVar as [Benign]. Clinvar id is 1282978.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAND1	NM_004821.3	c.543+70A>G		intron_variant		ENST00000231121.3
HAND1	XM_005268531.2	c.543+70A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAND1	ENST00000231121.3	c.543+70A>G		intron_variant		1	NM_004821.3	P1

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2579 AN: 152168 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0206

GnomAD4 exome AF: 0.00186 AC: 1987 AN: 1065502 Hom.: 41 AF XY: 0.00161 AC XY: 881 AN XY: 547854

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.00434

Gnomad4 ASJ exome AF: 0.0000423

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000268

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000928

Gnomad4 OTH exome AF: 0.00367

GnomAD4 genome AF: 0.0170 AC: 2582 AN: 152286 Hom.: 58 Cov.: 32 AF XY: 0.0164 AC XY: 1225 AN XY: 74472

Gnomad4 AFR AF: 0.0578

Gnomad4 AMR AF: 0.00817

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0122 Hom.: 5

Bravo AF: 0.0196

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.9
Dann	Benign	0.50

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

Other links and lift over

dbSNP: rs112556829; hg19: chr5-153856956;