rs17671387

Variant names:

• chr5-131548303-T-C
• rs17671387
• NM_016340.6:c.352-113A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-131548303-T-C
• chr5-131548303-T-G

Variant summary

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

The NM_016340.6(RAPGEF6):​c.352-113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,056,186 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 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: RAPGEF6 NM_016340.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 5 publications found

Genes affected

RAPGEF6 (HGNC:20655): (Rap guanine nucleotide exchange factor 6) Enables several functions, including GTP-dependent protein binding activity; guanyl-nucleotide exchange factor activity; and phosphatidic acid binding activity. Involved in microvillus assembly; positive regulation of GTPase activity; and protein localization to plasma membrane. Located in several cellular components, including apical plasma membrane; centrosome; and endocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000273217 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016340.6. 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
	RAPGEF6	NM_016340.6	MANE Select	c.352-113A>G		intron	N/A	NP_057424.3
	RAPGEF6	NM_001164386.2		c.352-113A>G		intron	N/A	NP_001157858.1
	RAPGEF6	NM_001164387.2		c.352-113A>G		intron	N/A	NP_001157859.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF6	ENST00000509018.6	TSL:1 MANE Select	c.352-113A>G		intron	N/A	ENSP00000421684.1
	ENSG00000273217	ENST00000514667.1	TSL:2	c.502-113A>G		intron	N/A	ENSP00000426948.1
	RAPGEF6	ENST00000296859.10	TSL:1	c.352-113A>G		intron	N/A	ENSP00000296859.6

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152172 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000885 AC: 8 AN: 903896 Hom.: 0 AF XY: 0.00000872 AC XY: 4 AN XY: 458644

African (AFR) AF: 0.00 AC: 0 AN: 21190

American (AMR) AF: 0.000254 AC: 6 AN: 23634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17460

East Asian (EAS) AF: 0.00 AC: 0 AN: 35090

South Asian (SAS) AF: 0.00 AC: 0 AN: 57528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3294

European-Non Finnish (NFE) AF: 0.00000300 AC: 2 AN: 665766

Other (OTH) AF: 0.00 AC: 0 AN: 41488

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152290 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 259

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.3
DANN	Benign	0.71
PhyloP100		0.064

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

Other links and lift over

dbSNP: rs17671387; hg19: chr5-130883996;