dbSNP rs1009948: XIST:n.11398-464G>A (chrX-73833838-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000429829.7(XIST):n.11398-464G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 112,963 control chromosomes in the GnomAD database, including 615 homozygotes. There are 2,871 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 0.094 ( 611 hom., 2839 hem., cov: 22)

Exomes 𝑓: 0.068 ( 4 hom. 32 hem. )

Consequence

XIST
ENST00000429829.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

1 publications found

Variant links:

Genes affected

XIST (HGNC:12810): (X inactive specific transcript) X inactivation is an early developmental process in mammalian females that transcriptionally silences one of the pair of X chromosomes, thus providing dosage equivalence between males and females. The process is regulated by several factors, including a region of chromosome X called the X inactivation center (XIC). The XIC comprises several non-coding and protein-coding genes, and this gene was the first non-coding gene identified within the XIC. This gene is expressed exclusively from the XIC of the inactive X chromosome, and is essential for the initiation and spread of X-inactivation. The transcript is a spliced RNA. Alternatively spliced transcript variants have been identified, but their full length sequences have not been determined. Mutations in the XIST promoter cause familial skewed X inactivation. [provided by RefSeq, Apr 2012]

XIST 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
XIST	NR_001564.3 link	n.11398-464G>A	intron_variant	Intron 2 of 5
XIST	NR_190997.1 link	n.11398-464G>A	intron_variant	Intron 2 of 7
XIST	NR_190998.1 link	n.2370-464G>A	intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
XIST	ENST00000429829.7 link	n.11398-464G>A	intron_variant	Intron 2 of 5	1
XIST	ENST00000421322.3 link	n.579-464G>A	intron_variant	Intron 2 of 6	2
XIST	ENST00000434839.3 link	n.165-464G>A	intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.0936

AC:

10390

AN:

110985

Hom.:

611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.0117

Gnomad AMR

AF:

0.0571

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0504

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.0798

Gnomad NFE

AF:

0.0528

Gnomad OTH

AF:

0.0860

GnomAD4 exome

AF:

0.0681

AC:

131

AN:

1925

Hom.:

AF XY:

0.256

AC XY:

AN XY:

125

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.0724

AC:

AN:

304

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0247

AC:

AN:

European-Finnish (FIN)

AF:

0.0227

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0677

AC:

AN:

1314

Other (OTH)

AF:

0.0833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0936

AC:

10393

AN:

111038

Hom.:

611

Cov.:

AF XY:

0.0853

AC XY:

2839

AN XY:

33286

show subpopulations

African (AFR)

AF:

0.208

AC:

6332

AN:

30430

American (AMR)

AF:

0.0569

AC:

596

AN:

10476

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

308

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3514

South Asian (SAS)

AF:

0.0506

AC:

133

AN:

2629

European-Finnish (FIN)

AF:

0.0126

AC:

AN:

5937

Middle Eastern (MID)

AF:

0.0737

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0528

AC:

2797

AN:

53007

Other (OTH)

AF:

0.0850

AC:

128

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

328

655

983

1310

1638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0741

Hom.:

3827

Bravo

AF:

0.103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.18

(source)

DANN

Benign

0.074

PhyloP100

-1.1

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