rs4072375

Positions:

• chr2-3539691-A-G

Variant summary

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

The NR_148532.2(RNASEH1):​n.1019-2780T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,024 control chromosomes in the GnomAD database, including 13,729 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 0.40 (13729 hom., cov: 31)
• Consequence: RNASEH1 NR_148532.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881

Genes affected

RNASEH1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEH1	NR_148532.2	n.1019-2780T>C		intron_variant, non_coding_transcript_variant
RNASEH1	NR_148534.2	n.1019-2780T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61365 AN: 151906 Hom.: 13701 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.404 AC: 61432 AN: 152024 Hom.: 13729 Cov.: 31 AF XY: 0.392 AC XY: 29135 AN XY: 74324

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.402

Alfa AF: 0.346 Hom.: 4233

Bravo AF: 0.418

Asia WGS AF: 0.281 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.40
DANN	Benign	0.17

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: rs4072375; hg19: chr2-3587281;