1-174921439-C-T

Variant names:

• chr1-174921439-C-T
• rs6693750
• NM_001366446.1:c.2341-36018C>T

Variant summary

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

The NM_001366446.1(RABGAP1L):​c.2341-36018C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 152,208 control chromosomes in the GnomAD database, including 397 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 0.061 (397 hom., cov: 32)
• Consequence: RABGAP1L NM_001366446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.084 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABGAP1L	NM_001366446.1	c.2341-36018C>T		intron_variant	Intron 19 of 25	ENST00000681986.1	NP_001353375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABGAP1L	ENST00000681986.1	c.2341-36018C>T		intron_variant	Intron 19 of 25		NM_001366446.1	ENSP00000507884.1

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 9266 AN: 152090 Hom.: 397 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0859

Gnomad OTH AF: 0.0485

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

GnomAD4 genome AF: 0.0609 AC: 9263 AN: 152208 Hom.: 397 Cov.: 32 AF XY: 0.0624 AC XY: 4644 AN XY: 74396

African (AFR) AF: 0.0159 AC: 662 AN: 41532

American (AMR) AF: 0.0503 AC: 770 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0546 AC: 264 AN: 4832

European-Finnish (FIN) AF: 0.110 AC: 1164 AN: 10562

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0859 AC: 5840 AN: 68014

Other (OTH) AF: 0.0475 AC: 100 AN: 2106

Alfa AF: 0.0714 Hom.: 218

Bravo AF: 0.0527

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.3
DANN	Benign	0.61
PhyloP100		-0.079
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: rs6693750; hg19: chr1-174890576;