1-174322812-C-G

Variant names:

• chr1-174322812-C-G
• rs10912765
• NM_001366446.1:c.1465+17685C>G

Variant summary

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

The NM_001366446.1(RABGAP1L):​c.1465+17685C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,902 control chromosomes in the GnomAD database, including 6,573 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 (6573 hom., cov: 32)
• Consequence: RABGAP1L NM_001366446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 3 publications found

Genes affected

RABGAP1L (HGNC:24663): (RAB GTPase activating protein 1 like) Enables GTPase activator activity and small GTPase binding activity. Acts upstream of or within regulation of protein localization. Located in Golgi apparatus; early endosome; and nucleus. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366446.1. 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
	RABGAP1L	NM_001366446.1	MANE Select	c.1465+17685C>G		intron	N/A	NP_001353375.1
	RABGAP1L	NM_001366448.1		c.1465+17685C>G		intron	N/A	NP_001353377.1
	RABGAP1L	NM_014857.5		c.1465+17685C>G		intron	N/A	NP_055672.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1L	ENST00000681986.1	MANE Select	c.1465+17685C>G		intron	N/A	ENSP00000507884.1
	RABGAP1L	ENST00000357444.10	TSL:1	c.1354+17685C>G		intron	N/A	ENSP00000350027.6
	RABGAP1L	ENST00000457696.1	TSL:1	c.1501+17685C>G		intron	N/A	ENSP00000403136.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42681 AN: 151784 Hom.: 6556 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.0679

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.281 AC: 42747 AN: 151902 Hom.: 6573 Cov.: 32 AF XY: 0.282 AC XY: 20897 AN XY: 74222

African (AFR) AF: 0.395 AC: 16343 AN: 41392

American (AMR) AF: 0.276 AC: 4210 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3464

East Asian (EAS) AF: 0.0684 AC: 354 AN: 5172

South Asian (SAS) AF: 0.219 AC: 1056 AN: 4820

European-Finnish (FIN) AF: 0.261 AC: 2742 AN: 10516

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15963 AN: 67960

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.257 Hom.: 775

Bravo AF: 0.288

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.92
DANN	Benign	0.70
PhyloP100		-1.3
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: rs10912765; hg19: chr1-174291950;