5-154477414-C-G

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+52G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,398,904 control chromosomes in the GnomAD database, including 80,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7388 hom., cov: 32)
  • Exomes 𝑓: 0.34 (72811 hom.)
• Consequence: HAND1 NM_004821.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.695

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=-0.84).
• BP6: Variant 5-154477414-C-G is Benign according to our data. Variant chr5-154477414-C-G is described in ClinVar as [Benign]. Clinvar id is 1273310.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAND1	NM_004821.3	c.543+52G>C		intron_variant		ENST00000231121.3
HAND1	XM_005268531.2	c.543+52G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAND1	ENST00000231121.3	c.543+52G>C		intron_variant		1	NM_004821.3	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45632 AN: 151990 Hom.: 7367 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.336 AC: 418504 AN: 1246796 Hom.: 72811 Cov.: 19 AF XY: 0.335 AC XY: 211167 AN XY: 630996

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.300 AC: 45685 AN: 152108 Hom.: 7388 Cov.: 32 AF XY: 0.303 AC XY: 22495 AN XY: 74356

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.308

Alfa AF: 0.317 Hom.: 1021

Bravo AF: 0.307

Asia WGS AF: 0.338 AC: 1175 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 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.0
Dann	Benign	0.77

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: rs1846966; hg19: chr5-153856974; COSMIC: COSV50562430;