rs4612544

Variant names:

• chrX-71106804-A-G
• rs4612544
• ENST00000646505.1:n.925-34T>C

Variant summary

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

The ENST00000646505.1(ENSG00000285171):​n.925-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 712,380 control chromosomes in the GnomAD database, including 4,433 homozygotes. There are 24,361 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 0.15 (1071 hom., 4573 hem., cov: 22)
  • Exomes 𝑓: 0.12 (3362 hom. 19788 hem.)
• Consequence: ENSG00000285171 ENST00000646505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682
• Publications: 1 publications found

Genes affected

ENSG00000285171 (HGNC:):

CXorf65 (HGNC:33713): (chromosome X open reading frame 65)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000646505.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXorf65	NM_001025265.3	MANE Select	c.-248T>C		upstream_gene	N/A	NP_001020436.1	A6NEN9
	CXorf65	NR_033212.2		n.-64T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285171	ENST00000646505.1		n.925-34T>C		intron	N/A	ENSP00000496673.1	A0A2R8YE73
	ENSG00000285171	ENST00000642473.1		n.1289-142T>C		intron	N/A
	ENSG00000285171	ENST00000644022.1		n.1191-101T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.148 AC: 16353 AN: 110765 Hom.: 1067 Cov.: 22

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.124 AC: 74300 AN: 601561 Hom.: 3362 Cov.: 9 AF XY: 0.151 AC XY: 19788 AN XY: 131425

African (AFR) AF: 0.263 AC: 4035 AN: 15344

American (AMR) AF: 0.104 AC: 1436 AN: 13846

Ashkenazi Jewish (ASJ) AF: 0.0719 AC: 807 AN: 11228

East Asian (EAS) AF: 0.111 AC: 2729 AN: 24501

South Asian (SAS) AF: 0.206 AC: 4939 AN: 24017

European-Finnish (FIN) AF: 0.115 AC: 2535 AN: 22133

Middle Eastern (MID) AF: 0.127 AC: 222 AN: 1754

European-Non Finnish (NFE) AF: 0.117 AC: 53838 AN: 460243

Other (OTH) AF: 0.132 AC: 3759 AN: 28495

GnomAD4 genome AF: 0.148 AC: 16375 AN: 110819 Hom.: 1071 Cov.: 22 AF XY: 0.138 AC XY: 4573 AN XY: 33081

African (AFR) AF: 0.247 AC: 7484 AN: 30332

American (AMR) AF: 0.110 AC: 1151 AN: 10481

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 192 AN: 2641

East Asian (EAS) AF: 0.122 AC: 432 AN: 3530

South Asian (SAS) AF: 0.189 AC: 488 AN: 2584

European-Finnish (FIN) AF: 0.105 AC: 625 AN: 5951

Middle Eastern (MID) AF: 0.106 AC: 23 AN: 216

European-Non Finnish (NFE) AF: 0.107 AC: 5671 AN: 52894

Other (OTH) AF: 0.143 AC: 216 AN: 1511

Alfa AF: 0.136 Hom.: 877

Bravo AF: 0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.6
DANN	Benign	0.87
PhyloP100		0.68
PromoterAI		0.17	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4612544;

hg19: chrX-70326654;

COSMIC: COSV52150492;