5-131557048-A-G

Variant names:

• chr5-131557048-A-G
• rs6873582
• NM_016340.6:c.351+4930T>C

Variant summary

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

The NM_001164386.2(RAPGEF6):​c.351+4930T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,108 control chromosomes in the GnomAD database, including 46,565 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 0.78 (46565 hom., cov: 31)
• Consequence: RAPGEF6 NM_001164386.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164386.2. 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
	RAPGEF6	NM_016340.6	MANE Select	c.351+4930T>C		intron	N/A	NP_057424.3
	RAPGEF6	NM_001164386.2		c.351+4930T>C		intron	N/A	NP_001157858.1
	RAPGEF6	NM_001164387.2		c.351+4930T>C		intron	N/A	NP_001157859.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF6	ENST00000509018.6	TSL:1 MANE Select	c.351+4930T>C		intron	N/A	ENSP00000421684.1
	ENSG00000273217	ENST00000514667.1	TSL:2	c.501+4930T>C		intron	N/A	ENSP00000426948.1
	RAPGEF6	ENST00000296859.10	TSL:1	c.351+4930T>C		intron	N/A	ENSP00000296859.6

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118499 AN: 151988 Hom.: 46535 Cov.: 31

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.780 AC: 118581 AN: 152108 Hom.: 46565 Cov.: 31 AF XY: 0.771 AC XY: 57284 AN XY: 74334

African (AFR) AF: 0.834 AC: 34597 AN: 41492

American (AMR) AF: 0.751 AC: 11490 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2496 AN: 3468

East Asian (EAS) AF: 0.503 AC: 2597 AN: 5166

South Asian (SAS) AF: 0.743 AC: 3585 AN: 4826

European-Finnish (FIN) AF: 0.639 AC: 6744 AN: 10558

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54498 AN: 67992

Other (OTH) AF: 0.790 AC: 1666 AN: 2110

Alfa AF: 0.786 Hom.: 7085

Bravo AF: 0.789

Asia WGS AF: 0.622 AC: 2163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.20
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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: rs6873582; hg19: chr5-130892741;