chrX-17478077-G-A

Variant names:

• chrX-17478077-G-A
• rs7473191
• NM_001291867.2:c.565+101755G>A

Variant summary

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

The NM_001291867.2(NHS):​c.565+101755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 111,478 control chromosomes in the GnomAD database, including 549 homozygotes. There are 1,802 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 0.061 (549 hom., 1802 hem., cov: 23)
• Consequence: NHS NM_001291867.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHS	NM_001291867.2	c.565+101755G>A		intron_variant	Intron 1 of 8	ENST00000676302.1	NP_001278796.1
NHS	NM_198270.4	c.565+101755G>A		intron_variant	Intron 1 of 7		NP_938011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1	c.565+101755G>A		intron_variant	Intron 1 of 8		NM_001291867.2	ENSP00000502262.1
NHS	ENST00000380060.7	c.565+101755G>A		intron_variant	Intron 1 of 7	1		ENSP00000369400.3

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 6834 AN: 111427 Hom.: 549 Cov.: 23

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000378

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.000847

Gnomad OTH AF: 0.0452

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

GnomAD4 genome AF: 0.0614 AC: 6845 AN: 111478 Hom.: 549 Cov.: 23 AF XY: 0.0535 AC XY: 1802 AN XY: 33694

African (AFR) AF: 0.214 AC: 6512 AN: 30500

American (AMR) AF: 0.0204 AC: 215 AN: 10524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3520

South Asian (SAS) AF: 0.000757 AC: 2 AN: 2641

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6083

Middle Eastern (MID) AF: 0.0138 AC: 3 AN: 217

European-Non Finnish (NFE) AF: 0.000847 AC: 45 AN: 53135

Other (OTH) AF: 0.0446 AC: 68 AN: 1523

Alfa AF: 0.0352 Hom.: 358

Bravo AF: 0.0711

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.67
PhyloP100		-0.12
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: rs7473191; hg19: chrX-17496200;