2-24623946-A-G

Variant names:

• chr2-24623946-A-G
• rs11677500
• NM_003743.5:c.-174-20020A>G

Variant summary

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

The NM_003743.5(NCOA1):​c.-174-20020A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,060 control chromosomes in the GnomAD database, including 19,378 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 0.48 (19378 hom., cov: 31)
• Consequence: NCOA1 NM_003743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 5 publications found

Genes affected

NCOA1 (HGNC:7668): (nuclear receptor coactivator 1) The protein encoded by this gene acts as a transcriptional coactivator for steroid and nuclear hormone receptors. It is a member of the p160/steroid receptor coactivator (SRC) family and like other family members has histone acetyltransferase activity and contains a nuclear localization signal, as well as bHLH and PAS domains. The product of this gene binds nuclear receptors directly and stimulates the transcriptional activities in a hormone-dependent fashion. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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 (AMR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA1	NM_003743.5	c.-174-20020A>G		intron_variant	Intron 3 of 22	ENST00000348332.8	NP_003734.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA1	ENST00000348332.8	c.-174-20020A>G		intron_variant	Intron 3 of 22	1	NM_003743.5	ENSP00000320940.5

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73500 AN: 151942 Hom.: 19363 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.484 AC: 73532 AN: 152060 Hom.: 19378 Cov.: 31 AF XY: 0.485 AC XY: 36051 AN XY: 74328

African (AFR) AF: 0.263 AC: 10917 AN: 41494

American (AMR) AF: 0.648 AC: 9907 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2117 AN: 3464

East Asian (EAS) AF: 0.558 AC: 2875 AN: 5154

South Asian (SAS) AF: 0.560 AC: 2700 AN: 4818

European-Finnish (FIN) AF: 0.518 AC: 5471 AN: 10568

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37895 AN: 67966

Other (OTH) AF: 0.541 AC: 1141 AN: 2108

Alfa AF: 0.536 Hom.: 58778

Bravo AF: 0.484

Asia WGS AF: 0.583 AC: 2024 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	0.70
DANN	Benign	0.53
PhyloP100		-0.015
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: rs11677500; hg19: chr2-24846815;