1-183843673-G-A

Variant names:

• chr1-183843673-G-A
• rs11806497
• NM_001297671.3:c.139-3893G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015149.6(RGL1):​c.244-3893G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0095 in 152,212 control chromosomes in the GnomAD database, including 22 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 0.0095 (22 hom., cov: 33)
• Consequence: RGL1 NM_015149.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 1 publications found

Genes affected

RGL1 (HGNC:30281): (ral guanine nucleotide dissociation stimulator like 1) Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0095 (1446/152212) while in subpopulation AFR AF = 0.0323 (1342/41522). AF 95% confidence interval is 0.0309. There are 22 homozygotes in GnomAd4. There are 706 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1446 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015149.6. 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
	RGL1	NM_001297671.3	MANE Select	c.139-3893G>A		intron	N/A	NP_001284600.1
	RGL1	NM_015149.6		c.244-3893G>A		intron	N/A	NP_055964.3
	RGL1	NM_001297669.3		c.133-3893G>A		intron	N/A	NP_001284598.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGL1	ENST00000360851.4	TSL:1 MANE Select	c.139-3893G>A		intron	N/A	ENSP00000354097.3
	RGL1	ENST00000304685.8	TSL:1	c.244-3893G>A		intron	N/A	ENSP00000303192.3
	RGL1	ENST00000888235.1		c.139-3893G>A		intron	N/A	ENSP00000558294.1

Frequencies

GnomAD3 genomes AF: 0.00949 AC: 1444 AN: 152094 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00719

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

GnomAD4 genome AF: 0.00950 AC: 1446 AN: 152212 Hom.: 22 Cov.: 33 AF XY: 0.00949 AC XY: 706 AN XY: 74418

African (AFR) AF: 0.0323 AC: 1342 AN: 41522

American (AMR) AF: 0.00301 AC: 46 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68008

Other (OTH) AF: 0.00712 AC: 15 AN: 2108

Alfa AF: 0.00257 Hom.: 0

Bravo AF: 0.0113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.66
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

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: rs11806497; hg19: chr1-183812807;