15-77454848-A-G

Position:

• chr15-77454848-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304504.2(HMG20A):​c.-4-3556A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,718 control chromosomes in the GnomAD database, including 30,377 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30377 hom., cov: 29)
• Consequence: HMG20A NM_001304504.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

Genes affected

HMG20A (HGNC:5001): (high mobility group 20A) Enables identical protein binding activity. Predicted to be involved in regulation of gene expression. Predicted to act upstream of or within negative regulation of neuron differentiation; negative regulation of protein sumoylation; and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMG20A	NM_001304504.2	c.-4-3556A>G		intron_variant		ENST00000336216.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMG20A	ENST00000336216.9	c.-4-3556A>G		intron_variant		1	NM_001304504.2	P1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94895 AN: 151600 Hom.: 30342 Cov.: 29

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.634

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.626 AC: 94986 AN: 151718 Hom.: 30377 Cov.: 29 AF XY: 0.618 AC XY: 45802 AN XY: 74126

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.638

Alfa AF: 0.686 Hom.: 48261

Bravo AF: 0.623

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.49

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: rs7178572; hg19: chr15-77747190;