8-23295747-T-G

Position:

• chr8-23295747-T-G

Variant summary

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

The NM_001136108.3(R3HCC1):​c.1193-220T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 609,670 control chromosomes in the GnomAD database, including 30,344 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 0.30 (7440 hom., cov: 33)
  • Exomes 𝑓: 0.30 (22904 hom.)
• Consequence: R3HCC1 NM_001136108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

Genes affected

R3HCC1 (HGNC:27329): (R3H domain and coiled-coil containing 1) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

R3HCC1 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HCC1	NM_001136108.3	c.1193-220T>G		intron_variant		ENST00000265806.12	NP_001129580.2
R3HCC1	NM_001301650.2	c.1067-220T>G		intron_variant			NP_001288579.1
R3HCC1	NR_125897.1	n.1162-220T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HCC1	ENST00000265806.12	c.1193-220T>G		intron_variant		1	NM_001136108.3	ENSP00000265806.8
R3HCC1	ENST00000625275.3	c.1067-220T>G		intron_variant		1		ENSP00000486278.2
R3HCC1	ENST00000522012.6	n.*472-220T>G		intron_variant		1		ENSP00000487121.2
R3HCC1	ENST00000411463.2	c.1313-220T>G		intron_variant		5		ENSP00000397555.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45877 AN: 152020 Hom.: 7431 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.304 AC: 139267 AN: 457532 Hom.: 22904 AF XY: 0.311 AC XY: 74510 AN XY: 239830

Gnomad4 AFR exome AF: 0.348

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.536

Gnomad4 SAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.302 AC: 45924 AN: 152138 Hom.: 7440 Cov.: 33 AF XY: 0.300 AC XY: 22344 AN XY: 74378

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.308

Alfa AF: 0.279 Hom.: 12388

Bravo AF: 0.305

Asia WGS AF: 0.467 AC: 1624 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	0.63
DANN	Benign	0.42

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: rs1002791; hg19: chr8-23153260; COSMIC: COSV56120973; COSMIC: COSV56120973;