rs7744005

Variant names:

• chr6-89404422-G-T
• rs7744005
• NM_021244.5:c.148+7424C>A

Variant summary

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

The NM_021244.5(RRAGD):​c.148+7424C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,016 control chromosomes in the GnomAD database, including 6,769 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 0.28 (6769 hom., cov: 31)
• Consequence: RRAGD NM_021244.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 6 publications found

Genes affected

RRAGD (HGNC:19903): (Ras related GTP binding D) RRAGD is a monomeric guanine nucleotide-binding protein, or G protein. By binding GTP or GDP, small G proteins act as molecular switches in numerous cell processes and signaling pathways.[supplied by OMIM, Apr 2004]

RRAGD Gene-Disease associations (from GenCC):

• hypomagnesemia 7, renal, with or without dilated cardiomyopathy

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRAGD	NM_021244.5	c.148+7424C>A		intron_variant	Intron 1 of 6	ENST00000369415.9	NP_067067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRAGD	ENST00000369415.9	c.148+7424C>A		intron_variant	Intron 1 of 6	1	NM_021244.5	ENSP00000358423.4
RRAGD	ENST00000359203.3	c.-10+7424C>A		intron_variant	Intron 1 of 5	2		ENSP00000352131.2
RRAGD	ENST00000492783.1	n.172+6912C>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42324 AN: 151898 Hom.: 6753 Cov.: 31

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.0741

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.279 AC: 42373 AN: 152016 Hom.: 6769 Cov.: 31 AF XY: 0.276 AC XY: 20494 AN XY: 74322

African (AFR) AF: 0.431 AC: 17867 AN: 41416

American (AMR) AF: 0.197 AC: 3016 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1038 AN: 3472

East Asian (EAS) AF: 0.0741 AC: 383 AN: 5170

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4816

European-Finnish (FIN) AF: 0.234 AC: 2472 AN: 10576

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.226 AC: 15340 AN: 67974

Other (OTH) AF: 0.269 AC: 567 AN: 2108

Alfa AF: 0.241 Hom.: 3581

Bravo AF: 0.282

Asia WGS AF: 0.207 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.81
PhyloP100		-1.2
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: rs7744005; hg19: chr6-90114141; COSMIC: COSV63270222;