chr1-174500767-T-C

Variant names:

• chr1-174500767-T-C
• rs12071794
• NM_001366446.1:c.1710+106622T>C

Variant summary

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

The NM_001366446.1(RABGAP1L):​c.1710+106622T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,880 control chromosomes in the GnomAD database, including 14,350 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 0.39 (14350 hom., cov: 31)
• Consequence: RABGAP1L NM_001366446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1L	NM_001366446.1	MANE Select	c.1710+106622T>C		intron	N/A	NP_001353375.1	A0A804HKD7
	RABGAP1L	NM_001366448.1		c.1710+106622T>C		intron	N/A	NP_001353377.1
	RABGAP1L	NM_014857.5		c.1710+106622T>C		intron	N/A	NP_055672.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABGAP1L	ENST00000681986.1	MANE Select	c.1710+106622T>C		intron	N/A	ENSP00000507884.1	A0A804HKD7
	RABGAP1L	ENST00000357444.10	TSL:1	c.1600-47070T>C		intron	N/A	ENSP00000350027.6	Q5R372-2
	RABGAP1L	ENST00000251507.8	TSL:2	c.1710+106622T>C		intron	N/A	ENSP00000251507.4	Q5R372-1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58809 AN: 151760 Hom.: 14321 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.0692

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.388 AC: 58903 AN: 151880 Hom.: 14350 Cov.: 31 AF XY: 0.385 AC XY: 28537 AN XY: 74198

African (AFR) AF: 0.690 AC: 28564 AN: 41406

American (AMR) AF: 0.328 AC: 5010 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1181 AN: 3468

East Asian (EAS) AF: 0.0697 AC: 360 AN: 5164

South Asian (SAS) AF: 0.252 AC: 1210 AN: 4808

European-Finnish (FIN) AF: 0.280 AC: 2951 AN: 10524

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18428 AN: 67942

Other (OTH) AF: 0.352 AC: 741 AN: 2108

Alfa AF: 0.293 Hom.: 11898

Bravo AF: 0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.7
DANN	Benign	0.65
PhyloP100		-0.40
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: rs12071794; hg19: chr1-174469905;