rs31251

Variant names:

• chr5-131498253-C-T
• rs31251
• NM_016340.6:c.1419+190G>A

Variant summary

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

The NM_016340.6(RAPGEF6):​c.1419+190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,010 control chromosomes in the GnomAD database, including 16,430 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 0.42 (16430 hom., cov: 32)
• Consequence: RAPGEF6 NM_016340.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 18 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAPGEF6	NM_016340.6	c.1419+190G>A		intron_variant	Intron 12 of 27	ENST00000509018.6	NP_057424.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPGEF6	ENST00000509018.6	c.1419+190G>A		intron_variant	Intron 12 of 27	1	NM_016340.6	ENSP00000421684.1
ENSG00000273217	ENST00000514667.1	c.1569+190G>A		intron_variant	Intron 13 of 28	2		ENSP00000426948.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63889 AN: 151892 Hom.: 16430 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.420 AC: 63891 AN: 152010 Hom.: 16430 Cov.: 32 AF XY: 0.419 AC XY: 31161 AN XY: 74292

African (AFR) AF: 0.110 AC: 4575 AN: 41472

American (AMR) AF: 0.513 AC: 7838 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1808 AN: 3464

East Asian (EAS) AF: 0.386 AC: 1994 AN: 5170

South Asian (SAS) AF: 0.507 AC: 2442 AN: 4820

European-Finnish (FIN) AF: 0.437 AC: 4602 AN: 10528

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38966 AN: 67962

Other (OTH) AF: 0.464 AC: 979 AN: 2108

Alfa AF: 0.517 Hom.: 62733

Bravo AF: 0.411

Asia WGS AF: 0.387 AC: 1336 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.65
DANN	Benign	0.50
PhyloP100		-0.66
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: rs31251; hg19: chr5-130833946;