rs7248026

Positions:

• chr19-46980746-T-G

Variant summary

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

The NM_004491.5(ARHGAP35):​c.3827-7243T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,070 control chromosomes in the GnomAD database, including 4,755 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 0.24 (4755 hom., cov: 32)
• Consequence: ARHGAP35 NM_004491.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

Genes affected

ARHGAP35 (HGNC:4591): (Rho GTPase activating protein 35) The human glucocorticoid receptor DNA binding factor, which associates with the promoter region of the glucocorticoid receptor gene (hGR gene), is a repressor of glucocorticoid receptor transcription. The amino acid sequence deduced from the cDNA sequences show the presence of three sequence motifs characteristic of a zinc finger and one motif suggestive of a leucine zipper in which 1 cysteine is found instead of all leucines. The GRLF1 enhances the homologous down-regulation of wild-type hGR gene expression. Biochemical analysis suggests that GRLF1 interaction is sequence specific and that transcriptional efficacy of GRLF1 is regulated through its interaction with specific sequence motif. The level of expression is regulated by glucocorticoids. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP35	NM_004491.5	c.3827-7243T>G		intron_variant		ENST00000672722.1
ARHGAP35	XM_024451473.2	c.3827-7243T>G		intron_variant
ARHGAP35	XR_002958305.2	n.4228-7243T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP35	ENST00000672722.1	c.3827-7243T>G		intron_variant			NM_004491.5	P1
ARHGAP35	ENST00000595822.1	n.90-7243T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37040 AN: 151952 Hom.: 4750 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.244 AC: 37063 AN: 152070 Hom.: 4755 Cov.: 32 AF XY: 0.236 AC XY: 17567 AN XY: 74352

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.0624

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.241

Alfa AF: 0.273 Hom.: 714

Bravo AF: 0.244

Asia WGS AF: 0.104 AC: 363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs7248026; hg19: chr19-47484003;