rs10482968

Positions:

• chr21-25763251-C-A
• chr21-25763251-C-T

Variant summary

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

The NM_002040.4(GABPA):​c.802+886C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 420,246 control chromosomes in the GnomAD database, including 3,172 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 0.10 (1008 hom., cov: 32)
  • Exomes 𝑓: 0.12 (2164 hom.)
• Consequence: GABPA NM_002040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

Genes affected

GABPA (HGNC:4071): (GA binding protein transcription factor subunit alpha) This gene encodes one of three GA-binding protein transcription factor subunits which functions as a DNA-binding subunit. Since this subunit shares identity with a subunit encoding the nuclear respiratory factor 2 gene, it is likely involved in activation of cytochrome oxidase expression and nuclear control of mitochondrial function. This subunit also shares identity with a subunit constituting the transcription factor E4TF1, responsible for expression of the adenovirus E4 gene. Because of its chromosomal localization and ability to form heterodimers with other polypeptides, this gene may play a role in the Down Syndrome phenotype. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2010]

LLPHP2 (HGNC:50492): (LLPH pseudogene 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABPA	NM_002040.4	c.802+886C>A		intron_variant		ENST00000400075.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABPA	ENST00000400075.4	c.802+886C>A		intron_variant		1	NM_002040.4	P1
GABPA	ENST00000354828.7	c.802+886C>A		intron_variant		1		P1
LLPHP2	ENST00000436405.1	n.83G>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15641 AN: 152004 Hom.: 1009 Cov.: 32

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.119 AC: 31851 AN: 268124 Hom.: 2164 Cov.: 0 AF XY: 0.118 AC XY: 18353 AN XY: 154896

Gnomad4 AFR exome AF: 0.0481

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.0945

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.103 AC: 15640 AN: 152122 Hom.: 1008 Cov.: 32 AF XY: 0.106 AC XY: 7848 AN XY: 74378

Gnomad4 AFR AF: 0.0511

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.115

Alfa AF: 0.105 Hom.: 1584

Bravo AF: 0.103

Asia WGS AF: 0.224 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.8
DANN	Benign	0.85

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: rs10482968; hg19: chr21-27135562; COSMIC: COSV61395387;