rs17780304

Positions:

• chr17-32208837-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001033566.3(RHOT1):​c.1739+528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 155,640 control chromosomes in the GnomAD database, including 131 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 0.032 (128 hom., cov: 32)
  • Exomes 𝑓: 0.039 (3 hom.)
• Consequence: RHOT1 NM_001033566.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.960

Genes affected

RHOT1 (HGNC:21168): (ras homolog family member T1) Predicted to enable GTP binding activity and GTPase activity. Involved in cellular homeostasis; mitochondrial outer membrane permeabilization; and mitochondrion transport along microtubule. Is integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0317 (4829/152122) while in subpopulation NFE AF= 0.0463 (3146/67988). AF 95% confidence interval is 0.0449. There are 128 homozygotes in gnomad4. There are 2408 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4829 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOT1	NM_001033566.3	c.1739+528G>A		intron_variant		ENST00000545287.7	NP_001028738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOT1	ENST00000545287.7	c.1739+528G>A		intron_variant		5	NM_001033566.3	ENSP00000439737.2

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4830 AN: 152004 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.00778

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0150

Gnomad FIN AF: 0.0783

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0206

GnomAD4 exome AF: 0.0387 AC: 136 AN: 3518 Hom.: 3 Cov.: 0 AF XY: 0.0380 AC XY: 71 AN XY: 1870

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0194

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0118

Gnomad4 FIN exome AF: 0.0938

Gnomad4 NFE exome AF: 0.0501

Gnomad4 OTH exome AF: 0.0606

GnomAD4 genome AF: 0.0317 AC: 4829 AN: 152122 Hom.: 128 Cov.: 32 AF XY: 0.0324 AC XY: 2408 AN XY: 74350

Gnomad4 AFR AF: 0.00775

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0150

Gnomad4 FIN AF: 0.0783

Gnomad4 NFE AF: 0.0463

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0425 Hom.: 32

Bravo AF: 0.0267

Asia WGS AF: 0.00578 AC: 21 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Benign	0.75

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: rs17780304; hg19: chr17-30535856;