rs7057398

Positions:

• chrX-106901299-T-C
• chrX-106901299-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138382.3(RIPPLY1):​c.296+175A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 111,094 control chromosomes in the GnomAD database, including 8,055 homozygotes. There are 13,184 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 0.40 (8055 hom., 13184 hem., cov: 23)
• Consequence: RIPPLY1 NM_138382.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878

Genes affected

RIPPLY1 (HGNC:25117): (ripply transcriptional repressor 1) This gene encodes a protein similar to a zebrafish protein which acts as a transcriptional repressor in and is required for somite segmentation in zebrafish embryos (PMID: 16326386). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

CLDN2 (HGNC:2041): (claudin 2) This gene product belongs to the claudin protein family whose members have been identified as major integral membrane proteins localized exclusively at tight junctions. Claudins are expressed in an organ-specific manner and regulate tissue-specific physiologic properties of tight junctions. This protein is expressed in the intestine. Alternatively spliced transcript variants with different 5' untranslated region have been found for this gene.[provided by RefSeq, Jan 2010]

MORC4 (HGNC:23485): (MORC family CW-type zinc finger 4) In human, the four current members of the microrchidia (morc) gene family share an N-terminal ATPase-like ATP-binding region and a CW four-cysteine zinc-finger motif. The protein encoded by this gene also has a nuclear matrix binding domain and a two-stranded coiled-coil motif near its C-terminus. This gene is widely expressed at low levels in normal tissues and has elevated expression in placenta and testis. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPPLY1	NM_138382.3	c.296+175A>G		intron_variant		ENST00000276173.5	NP_612391.1
CLDN2	NM_001171092.1	c.-179+795T>C		intron_variant			NP_001164563.1
RIPPLY1	NM_001171706.2	c.156-391A>G		intron_variant			NP_001165177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPPLY1	ENST00000276173.5	c.296+175A>G		intron_variant		1	NM_138382.3	ENSP00000276173	P1
RIPPLY1	ENST00000411805.1	c.156-391A>G		intron_variant		1		ENSP00000400539
CLDN2	ENST00000541806.6	c.-179+795T>C		intron_variant		1		ENSP00000441283	P1
MORC4	ENST00000604604.1	c.112-85513A>G		intron_variant		2		ENSP00000474750

Frequencies

GnomAD3 genomes AF: 0.404 AC: 44837 AN: 111043 Hom.: 8050 Cov.: 23 AF XY: 0.394 AC XY: 13122 AN XY: 33273

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.404 AC: 44908 AN: 111094 Hom.: 8055 Cov.: 23 AF XY: 0.396 AC XY: 13184 AN XY: 33334

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.364

Alfa AF: 0.301 Hom.: 12063

Bravo AF: 0.415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.45

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

Other links and lift over

dbSNP: rs7057398; hg19: chrX-106144529; COSMIC: COSV52175035;