1-174500767-T-C

Position:

• chr1-174500767-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RABGAP1L	NM_001366446.1	c.1710+106622T>C		intron_variant		ENST00000681986.1	NP_001353375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RABGAP1L	ENST00000681986.1	c.1710+106622T>C		intron_variant			NM_001366446.1	ENSP00000507884	P2

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

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.0697

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.352

Alfa AF: 0.276 Hom.: 8040

Bravo AF: 0.404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.7
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs12071794; hg19: chr1-174469905;