rs3812430

Variant names:

• chr8-70138137-C-A
• rs3812430
• NM_006540.4:c.3158+66G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-70138137-C-A
• chr8-70138137-C-G
• chr8-70138137-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006540.4(NCOA2):​c.3158+66G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,532,942 control chromosomes in the GnomAD database, including 31,655 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 0.26 (7405 hom., cov: 33)
  • Exomes 𝑓: 0.16 (24250 hom.)
• Consequence: NCOA2 NM_006540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 11 publications found

Genes affected

NCOA2 (HGNC:7669): (nuclear receptor coactivator 2) The protein encoded by this gene functions as a transcriptional coactivator for nuclear hormone receptors, including steroid, thyroid, retinoid, and vitamin D receptors. The encoded protein acts as an intermediary factor for the ligand-dependent activity of these nuclear receptors, which regulate their target genes upon binding of cognate response elements. This gene has been found to be involved in translocations that result in fusions with other genes in various cancers, including the lysine acetyltransferase 6A (KAT6A) gene in acute myeloid leukemia, the ETS variant 6 (ETV6) gene in acute lymphoblastic leukemia, and the hes related family bHLH transcription factor with YRPW motif 1 (HEY1) gene in mesenchymal chondrosarcoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA2	NM_006540.4	c.3158+66G>T		intron_variant	Intron 15 of 22	ENST00000452400.7	NP_006531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA2	ENST00000452400.7	c.3158+66G>T		intron_variant	Intron 15 of 22	1	NM_006540.4	ENSP00000399968.2
NCOA2	ENST00000522054.1	n.255G>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
NCOA2	ENST00000518363.2	c.533+66G>T		intron_variant	Intron 3 of 10	2		ENSP00000429132.2
NCOA2	ENST00000518287.6	n.*115+66G>T		intron_variant	Intron 14 of 20	5		ENSP00000430148.2

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39096 AN: 151972 Hom.: 7378 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.159 AC: 220052 AN: 1380852 Hom.: 24250 Cov.: 26 AF XY: 0.163 AC XY: 111660 AN XY: 686718

African (AFR) AF: 0.528 AC: 15949 AN: 30224

American (AMR) AF: 0.142 AC: 4695 AN: 33178

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 4090 AN: 22560

East Asian (EAS) AF: 0.516 AC: 20169 AN: 39054

South Asian (SAS) AF: 0.309 AC: 23727 AN: 76736

European-Finnish (FIN) AF: 0.121 AC: 6263 AN: 51672

Middle Eastern (MID) AF: 0.193 AC: 1047 AN: 5420

European-Non Finnish (NFE) AF: 0.125 AC: 133081 AN: 1064956

Other (OTH) AF: 0.193 AC: 11031 AN: 57052

GnomAD4 genome AF: 0.258 AC: 39172 AN: 152090 Hom.: 7405 Cov.: 33 AF XY: 0.258 AC XY: 19153 AN XY: 74362

African (AFR) AF: 0.509 AC: 21116 AN: 41470

American (AMR) AF: 0.171 AC: 2617 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3472

East Asian (EAS) AF: 0.528 AC: 2724 AN: 5160

South Asian (SAS) AF: 0.329 AC: 1586 AN: 4816

European-Finnish (FIN) AF: 0.119 AC: 1264 AN: 10600

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8625 AN: 67980

Other (OTH) AF: 0.230 AC: 485 AN: 2110

Alfa AF: 0.141 Hom.: 1170

Bravo AF: 0.269

Asia WGS AF: 0.406 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.46
PhyloP100		-0.34
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: rs3812430; hg19: chr8-71050372; COSMIC: COSV51219707;