Variant 10-46011178-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001145263.2(NCOA4):c.743A>G(p.Asn248Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00276 in 1,597,058 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 28 hom. )

Consequence

NCOA4
NM_001145263.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.113

Variant links:

Genes affected

NCOA4 (HGNC:7671): (nuclear receptor coactivator 4) This gene encodes an androgen receptor coactivator. The encoded protein interacts with the androgen receptor in a ligand-dependent manner to enhance its transcriptional activity. Chromosomal translocations between this gene and the ret tyrosine kinase gene, also located on chromosome 10, have been associated with papillary thyroid carcinoma. Alternatively spliced transcript variants have been described. Pseudogenes are present on chromosomes 4, 5, 10, and 14. [provided by RefSeq, Feb 2009]

NCOA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031405091).

BP6

Variant 10-46011178-T-C is Benign according to our data. Variant chr10-46011178-T-C is described in ClinVar as [Benign]. Clinvar id is 714453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00507 (772/152326) while in subpopulation EAS AF= 0.021 (109/5192). AF 95% confidence interval is 0.0178. There are 6 homozygotes in gnomad4. There are 370 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA4	NM_001145263.2 linkuse as main transcript	c.743A>G	p.Asn248Ser	missense_variant	8/10	ENST00000581486.6	NP_001138735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6 linkuse as main transcript	c.743A>G	p.Asn248Ser	missense_variant	8/10	1	NM_001145263.2	ENSP00000462943	P2	Q13772-1

Frequencies

GnomAD3 genomes

AF:

0.00507

AC:

772

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00693

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0211

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00522

AC:

1223

AN:

234120

Hom.:

AF XY:

0.00451

AC XY:

573

AN XY:

126968

show subpopulations

Gnomad AFR exome

AF:

0.00905

Gnomad AMR exome

AF:

0.0125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0218

Gnomad SAS exome

AF:

0.00640

Gnomad FIN exome

AF:

0.000429

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00450

GnomAD4 exome

AF:

0.00252

AC:

3635

AN:

1444732

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

1848

AN XY:

718738

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0000800

Gnomad4 EAS exome

AF:

0.0148

Gnomad4 SAS exome

AF:

0.00642

Gnomad4 FIN exome

AF:

0.000378

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.00484

GnomAD4 genome

AF:

0.00507

AC:

772

AN:

152326

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

370

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.00692

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0210

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.00620

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.14

DANN

Benign

0.62

DEOGEN2

Benign

0.031

T;T;T;T;.;.;.

LIST_S2

Benign

0.31

.;T;T;.;T;T;T

MetaRNN

Benign

0.0031

T;T;T;T;T;T;T

Sift4G

Benign

0.73

T;T;T;T;T;T;T

Vest4

0.025

gMVP

0.072

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over