rs10482968

Variant names:

• chr21-25763251-C-A
• rs10482968
• NM_002040.4:c.802+886C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002040.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABPA	NM_002040.4	MANE Select	c.802+886C>A		intron	N/A	NP_002031.2
	GABPA	NM_001197297.2		c.802+886C>A		intron	N/A	NP_001184226.1	Q06546

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABPA	ENST00000400075.4	TSL:1 MANE Select	c.802+886C>A		intron	N/A	ENSP00000382948.3	Q06546
	GABPA	ENST00000354828.7	TSL:1	c.802+886C>A		intron	N/A	ENSP00000346886.3	Q06546
	GABPA	ENST00000924594.1		c.802+886C>A		intron	N/A	ENSP00000594653.1

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

African (AFR) AF: 0.0481 AC: 280 AN: 5820

American (AMR) AF: 0.155 AC: 2694 AN: 17404

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 623 AN: 6594

East Asian (EAS) AF: 0.304 AC: 3343 AN: 10994

South Asian (SAS) AF: 0.133 AC: 5043 AN: 37804

European-Finnish (FIN) AF: 0.123 AC: 3257 AN: 26550

Middle Eastern (MID) AF: 0.0914 AC: 77 AN: 842

European-Non Finnish (NFE) AF: 0.101 AC: 15157 AN: 149630

Other (OTH) AF: 0.110 AC: 1377 AN: 12486

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

African (AFR) AF: 0.0511 AC: 2120 AN: 41508

American (AMR) AF: 0.137 AC: 2088 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3468

East Asian (EAS) AF: 0.298 AC: 1542 AN: 5176

South Asian (SAS) AF: 0.147 AC: 708 AN: 4820

European-Finnish (FIN) AF: 0.118 AC: 1247 AN: 10600

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7286 AN: 67972

Other (OTH) AF: 0.115 AC: 241 AN: 2104

Alfa AF: 0.104 Hom.: 2543

Bravo AF: 0.103

Asia WGS AF: 0.224 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.8
DANN	Benign	0.85
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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