Genetic Variant ENSG00000285171:n.925-34T>C (chrX-71106804-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000646505.1(ENSG00000285171):n.925-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 712,380 control chromosomes in the GnomAD database, including 4,433 homozygotes. There are 24,361 hemizygotes in GnomAD. 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 0.15 ( 1071 hom., 4573 hem., cov: 22)

Exomes 𝑓: 0.12 ( 3362 hom. 19788 hem. )

Consequence

ENSG00000285171
ENST00000646505.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.682

Publications

1 publications found

Variant links:

COSMIC-nc: COSV52150492

Genes affected

ENSG00000285171 (HGNC:):

ENSG00000285171 links:

CXorf65 (HGNC:33713): (chromosome X open reading frame 65)

CXorf65 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CXorf65	NM_001025265.3 link	c.-248T>C	upstream_gene_variant	ENST00000374251.6	NP_001020436.1	A6NEN9
CXorf65	NR_033212.2 link	n.-64T>C	upstream_gene_variant
CXorf65	XM_005262244.5 link	c.-248T>C	upstream_gene_variant		XP_005262301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285171	ENST00000646505.1 link	n.925-34T>C		intron_variant	Intron 7 of 11			ENSP00000496673.1		A0A2R8YE73
CXorf65	ENST00000374251.6 link	c.-248T>C		upstream_gene_variant		5	NM_001025265.3	ENSP00000363369.4		A6NEN9

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

16353

AN:

110765

Hom.:

1067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0727

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.133

GnomAD4 exome

AF:

0.124

AC:

74300

AN:

601561

Hom.:

3362

Cov.:

AF XY:

0.151

AC XY:

19788

AN XY:

131425

show subpopulations

African (AFR)

AF:

0.263

AC:

4035

AN:

15344

American (AMR)

AF:

0.104

AC:

1436

AN:

13846

Ashkenazi Jewish (ASJ)

AF:

0.0719

AC:

807

AN:

11228

East Asian (EAS)

AF:

0.111

AC:

2729

AN:

24501

South Asian (SAS)

AF:

0.206

AC:

4939

AN:

24017

European-Finnish (FIN)

AF:

0.115

AC:

2535

AN:

22133

Middle Eastern (MID)

AF:

0.127

AC:

222

AN:

1754

European-Non Finnish (NFE)

AF:

0.117

AC:

53838

AN:

460243

Other (OTH)

AF:

0.132

AC:

3759

AN:

28495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2476

4952

7427

9903

12379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1936

3872

5808

7744

9680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.148

AC:

16375

AN:

110819

Hom.:

1071

Cov.:

AF XY:

0.138

AC XY:

4573

AN XY:

33081

show subpopulations

African (AFR)

AF:

0.247

AC:

7484

AN:

30332

American (AMR)

AF:

0.110

AC:

1151

AN:

10481

Ashkenazi Jewish (ASJ)

AF:

0.0727

AC:

192

AN:

2641

East Asian (EAS)

AF:

0.122

AC:

432

AN:

3530

South Asian (SAS)

AF:

0.189

AC:

488

AN:

2584

European-Finnish (FIN)

AF:

0.105

AC:

625

AN:

5951

Middle Eastern (MID)

AF:

0.106

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.107

AC:

5671

AN:

52894

Other (OTH)

AF:

0.143

AC:

216

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

494

988

1482

1976

2470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.136

Hom.:

877

Bravo

AF:

0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.6

(source)

DANN

Benign

0.87

PhyloP100

0.68

PromoterAI

0.17

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over