rs6527811

Variant names:

• chrX-17578848-G-T
• rs6527811
• NM_001291867.2:c.566-108894G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291867.2(NHS):​c.566-108894G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 111,329 control chromosomes in the GnomAD database, including 5,907 homozygotes. There are 6,771 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 0.22 (5907 hom., 6771 hem., cov: 23)
• Consequence: NHS NM_001291867.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 1 publications found

Genes affected

NHS (HGNC:7820): (NHS actin remodeling regulator) This gene encodes a protein containing four conserved nuclear localization signals. The encoded protein functions in eye, tooth, craniofacial and brain development, and it can regulate actin remodeling and cell morphology. Mutations in this gene have been shown to cause Nance-Horan syndrome, and also X-linked cataract-40. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2014]

NHS Gene-Disease associations (from GenCC):

• Nance-Horan syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000235834 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHS	NM_001291867.2	c.566-108894G>T		intron_variant	Intron 1 of 8	ENST00000676302.1	NP_001278796.1
NHS	NM_198270.4	c.566-108894G>T		intron_variant	Intron 1 of 7		NP_938011.1
LOC101928389	NR_135631.1	n.325-7083G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1	c.566-108894G>T		intron_variant	Intron 1 of 8		NM_001291867.2	ENSP00000502262.1
NHS	ENST00000380060.7	c.566-108894G>T		intron_variant	Intron 1 of 7	1		ENSP00000369400.3
ENSG00000235834	ENST00000433228.1	n.325-7083G>T		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 24326 AN: 111271 Hom.: 5899 Cov.: 23

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0763

Gnomad NFE AF: 0.00489

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.219 AC: 24407 AN: 111329 Hom.: 5907 Cov.: 23 AF XY: 0.202 AC XY: 6771 AN XY: 33563

African (AFR) AF: 0.718 AC: 21813 AN: 30378

American (AMR) AF: 0.154 AC: 1619 AN: 10482

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 50 AN: 2637

East Asian (EAS) AF: 0.0385 AC: 136 AN: 3531

South Asian (SAS) AF: 0.0818 AC: 218 AN: 2664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6043

Middle Eastern (MID) AF: 0.0837 AC: 18 AN: 215

European-Non Finnish (NFE) AF: 0.00489 AC: 260 AN: 53185

Other (OTH) AF: 0.194 AC: 293 AN: 1509

Alfa AF: 0.204 Hom.: 1852

Bravo AF: 0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.012
DANN	Benign	0.48
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs6527811; hg19: chrX-17596969;