Variant rs181143203 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_000451.4(SHOX):c.278-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 1,612,738 control chromosomes in the GnomAD database, including 9 homozygotes. There are 316 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., 34 hem., cov: 32)

Exomes 𝑓: 0.00038 ( 9 hom. 282 hem. )

Consequence

SHOX
NM_000451.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.874

Variant links:

Genes affected

SHOX (HGNC:10853): (SHOX homeobox) This gene belongs to the paired homeobox family and is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes. Defects in this gene are associated with idiopathic growth retardation and in the short stature phenotype of Turner syndrome patients. This gene is highly conserved across species from mammals to fish to flies. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

SHOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-634603-C-A is Benign according to our data. Variant chrX-634603-C-A is described in ClinVar as [Benign]. Clinvar id is 256194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-634603-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000368 (56/152320) while in subpopulation EAS AF= 0.0106 (55/5180). AF 95% confidence interval is 0.00838. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 34 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHOX	NM_000451.4 link	c.278-15C>A		intron_variant		ENST00000686671.1	NP_000442.1	O15266-1A0A024R385
SHOX	NM_006883.2 link	c.278-15C>A		intron_variant			NP_006874.1	O15266-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SHOX	ENST00000686671.1 link	c.278-15C>A	intron_variant		NM_000451.4	ENSP00000508521.1	O15266-1
SHOX	ENST00000381575.6 link	c.278-15C>A	intron_variant	1		ENSP00000370987.1	O15266-2
SHOX	ENST00000381578.6 link	c.278-15C>A	intron_variant	5		ENSP00000370990.1	O15266-1
SHOX	ENST00000334060.8 link	c.278-15C>A	intron_variant	5		ENSP00000335505.3	O15266-2

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74360

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00117

AC:

291

AN:

248876

Hom.:

AF XY:

0.00102

AC XY:

138

AN XY:

134898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0155

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000382

AC:

558

AN:

1460418

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

282

AN XY:

726434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0124

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.000614

GnomAD4 genome

AF:

0.000368

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0106

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000650

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 21, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.8

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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