2-172727878-C-T

Variant names:

• chr2-172727878-C-T
• rs1349498
• ENST00000435328.1:n.378-445G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000435328.1(RAPGEF4-AS1):​n.378-445G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,002 control chromosomes in the GnomAD database, including 3,378 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 0.20 (3378 hom., cov: 33)
• Consequence: RAPGEF4-AS1 ENST00000435328.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10
• Publications: 3 publications found

Genes affected

RAPGEF4-AS1 (HGNC:28081): (RAPGEF4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435328.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF4-AS1	NR_026995.1		n.378-445G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF4-AS1	ENST00000435328.1	TSL:1	n.378-445G>A		intron	N/A
	RAPGEF4-AS1	ENST00000455435.2	TSL:3	n.361+6427G>A		intron	N/A
	RAPGEF4-AS1	ENST00000773796.1		n.334+6427G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29690 AN: 151884 Hom.: 3370 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.196 AC: 29727 AN: 152002 Hom.: 3378 Cov.: 33 AF XY: 0.203 AC XY: 15117 AN XY: 74286

African (AFR) AF: 0.152 AC: 6283 AN: 41436

American (AMR) AF: 0.192 AC: 2934 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3468

East Asian (EAS) AF: 0.534 AC: 2762 AN: 5176

South Asian (SAS) AF: 0.200 AC: 963 AN: 4812

European-Finnish (FIN) AF: 0.296 AC: 3118 AN: 10534

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.185 AC: 12585 AN: 67974

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.187 Hom.: 11956

Bravo AF: 0.186

Asia WGS AF: 0.316 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.010
DANN	Benign	0.49
PhyloP100		-3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1349498;

hg19: chr2-173592606;