Variant chrX-152850430-G-A 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_015922.3(NSDHL):c.267+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000685 in 1,208,037 control chromosomes in the GnomAD database, including 3 homozygotes. There are 281 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., 41 hem., cov: 23)

Exomes 𝑓: 0.00067 ( 3 hom. 240 hem. )

Consequence

NSDHL
NM_015922.3 splice_region, intron

Scores

Splicing: ADA: 0.0001858

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.835

Variant links:

Genes affected

NSDHL (HGNC:13398): (NAD(P) dependent steroid dehydrogenase-like) The protein encoded by this gene is localized in the endoplasmic reticulum and is involved in cholesterol biosynthesis. Mutations in this gene are associated with CHILD syndrome, which is a X-linked dominant disorder of lipid metabolism with disturbed cholesterol biosynthesis, and typically lethal in males. Alternatively spliced transcript variants with differing 5' UTR have been found for this gene. [provided by RefSeq, Jul 2008]

NSDHL 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 (BayesDel_noAF=-0.84).

BP6

Variant X-152850430-G-A is Benign according to our data. Variant chrX-152850430-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 211749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000837 (94/112358) while in subpopulation NFE AF= 0.000957 (51/53282). AF 95% confidence interval is 0.000748. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 41 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
NSDHL	NM_015922.3 linkuse as main transcript	c.267+7G>A	splice_region_variant, intron_variant	ENST00000370274.8
NSDHL	NM_001129765.2 linkuse as main transcript	c.267+7G>A	splice_region_variant, intron_variant
NSDHL	XM_011531178.3 linkuse as main transcript	c.267+7G>A	splice_region_variant, intron_variant
NSDHL	XM_017029564.2 linkuse as main transcript	c.315+7G>A	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
NSDHL	ENST00000370274.8 linkuse as main transcript	c.267+7G>A	splice_region_variant, intron_variant	1	NM_015922.3	P1
NSDHL	ENST00000432467.1 linkuse as main transcript	c.267+7G>A	splice_region_variant, intron_variant	3
NSDHL	ENST00000440023.5 linkuse as main transcript	c.267+7G>A	splice_region_variant, intron_variant	5		P1

Frequencies

GnomAD3 genomes

AF:

0.000837

AC:

AN:

112303

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

34451

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000566

Gnomad ASJ

AF:

0.00188

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00506

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000957

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00140

AC:

257

AN:

183209

Hom.:

AF XY:

0.00118

AC XY:

AN XY:

67693

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000766

Gnomad ASJ exome

AF:

0.00241

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00762

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000669

AC:

733

AN:

1095679

Hom.:

Cov.:

AF XY:

0.000665

AC XY:

240

AN XY:

361075

show subpopulations

Gnomad4 AFR exome

AF:

0.0000759

Gnomad4 AMR exome

AF:

0.000625

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00666

Gnomad4 NFE exome

AF:

0.000438

Gnomad4 OTH exome

AF:

0.000739

GnomAD4 genome

AF:

0.000837

AC:

AN:

112358

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

34516

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.000566

Gnomad4 ASJ

AF:

0.00188

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00506

Gnomad4 NFE

AF:

0.000957

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.000461

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 28, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.3

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.0

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

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