rs10518839

Variant names:

• chr15-56192165-T-A
• rs10518839
• NM_022841.7:c.162-12862A>T

Variant summary

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

The NM_022841.7(RFX7):​c.162-12862A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,104 control chromosomes in the GnomAD database, including 1,651 homozygotes. 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 0.13 (1651 hom., cov: 31)
• Consequence: RFX7 NM_022841.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997
• Publications: 7 publications found

Genes affected

RFX7 (HGNC:25777): (regulatory factor X7) RFX7 is a member of the regulatory factor X (RFX) family of transcription factors (see RFX1, MIM 600006) (Aftab et al., 2008 [PubMed 18673564]).[supplied by OMIM, Mar 2009]

RFX7 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LOC390586 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFX7	NM_022841.7	c.162-12862A>T		intron_variant	Intron 2 of 9	ENST00000559447.8	NP_073752.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFX7	ENST00000559447.8	c.162-12862A>T		intron_variant	Intron 2 of 9	5	NM_022841.7	ENSP00000453281.3
RFX7	ENST00000673997.1	c.-96-47682A>T		intron_variant	Intron 2 of 8			ENSP00000501278.1
RFX7	ENST00000674082.1	c.-130-12862A>T		intron_variant	Intron 4 of 11			ENSP00000501248.1
ENSG00000261072	ENST00000565846.2	n.*188A>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19634 AN: 151986 Hom.: 1652 Cov.: 31

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.129 AC: 19645 AN: 152104 Hom.: 1651 Cov.: 31 AF XY: 0.133 AC XY: 9861 AN XY: 74340

African (AFR) AF: 0.0866 AC: 3593 AN: 41502

American (AMR) AF: 0.134 AC: 2048 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 699 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2249 AN: 5158

South Asian (SAS) AF: 0.306 AC: 1471 AN: 4808

European-Finnish (FIN) AF: 0.0830 AC: 879 AN: 10594

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8216 AN: 67986

Other (OTH) AF: 0.162 AC: 341 AN: 2108

Alfa AF: 0.116 Hom.: 159

Bravo AF: 0.130

Asia WGS AF: 0.316 AC: 1100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		1.0
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: rs10518839; hg19: chr15-56484363;