rs757281

Variant names:

• chr12-47748635-C-A
• rs757281
• NM_001098531.4:c.1155-93G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-47748635-C-A
• chr12-47748635-C-G
• chr12-47748635-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001098531.4(RAPGEF3):​c.1155-93G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000516 in 1,240,772 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: RAPGEF3 NM_001098531.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 7 publications found

Genes affected

RAPGEF3 (HGNC:16629): (Rap guanine nucleotide exchange factor 3) Enables guanyl-nucleotide exchange factor activity and protein domain specific binding activity. Involved in several processes, including positive regulation of protein modification process; regulation of actin cytoskeleton organization; and regulation of syncytium formation by plasma membrane fusion. Located in filopodium; lamellipodium; and microvillus. Colocalizes with cortical actin cytoskeleton and plasma membrane. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098531.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF3	NM_001098531.4	MANE Select	c.1155-93G>T		intron	N/A	NP_001092001.2
	RAPGEF3	NM_001098532.2		c.1029-93G>T		intron	N/A	NP_001092002.1
	RAPGEF3	NM_006105.5		c.1029-93G>T		intron	N/A	NP_006096.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF3	ENST00000449771.7	TSL:2 MANE Select	c.1155-93G>T		intron	N/A	ENSP00000395708.2
	RAPGEF3	ENST00000389212.7	TSL:2	c.1155-93G>T		intron	N/A	ENSP00000373864.3
	RAPGEF3	ENST00000549151.5	TSL:5	c.1029-93G>T		intron	N/A	ENSP00000448619.1

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000496 AC: 54 AN: 1088704 Hom.: 0 Cov.: 14 AF XY: 0.0000490 AC XY: 27 AN XY: 550802

African (AFR) AF: 0.00 AC: 0 AN: 26196

American (AMR) AF: 0.000274 AC: 10 AN: 36486

Ashkenazi Jewish (ASJ) AF: 0.000840 AC: 18 AN: 21440

East Asian (EAS) AF: 0.00 AC: 0 AN: 37110

South Asian (SAS) AF: 0.00 AC: 0 AN: 72420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4952

European-Non Finnish (NFE) AF: 0.0000253 AC: 20 AN: 792054

Other (OTH) AF: 0.000126 AC: 6 AN: 47630

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 152068 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74268

African (AFR) AF: 0.00 AC: 0 AN: 41374

American (AMR) AF: 0.000393 AC: 6 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 2355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.13
PhyloP100		-0.72

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

Other links and lift over

dbSNP: rs757281; hg19: chr12-48142418;