16-611335-T-C

Variant names:

• chr16-611335-T-C
• rs7204439
• NM_021168.5:c.143-5873T>C

Variant summary

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

The NM_021168.5(RAB40C):​c.143-5873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,078 control chromosomes in the GnomAD database, including 18,651 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 0.49 (18651 hom., cov: 32)
• Consequence: RAB40C NM_021168.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 17 publications found

Genes affected

RAB40C (HGNC:18285): (RAB40C, member RAS oncogene family) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in protein localization to plasma membrane. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in endosome; plasma membrane; and synaptic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

LOC124903618 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB40C	NM_021168.5	c.143-5873T>C		intron_variant	Intron 1 of 5	ENST00000248139.8	NP_066991.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB40C	ENST00000248139.8	c.143-5873T>C		intron_variant	Intron 1 of 5	1	NM_021168.5	ENSP00000248139.3

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74049 AN: 151960 Hom.: 18603 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.488 AC: 74154 AN: 152078 Hom.: 18651 Cov.: 32 AF XY: 0.494 AC XY: 36760 AN XY: 74342

African (AFR) AF: 0.567 AC: 23530 AN: 41488

American (AMR) AF: 0.499 AC: 7634 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1326 AN: 3472

East Asian (EAS) AF: 0.635 AC: 3274 AN: 5154

South Asian (SAS) AF: 0.624 AC: 3015 AN: 4832

European-Finnish (FIN) AF: 0.505 AC: 5350 AN: 10584

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.422 AC: 28667 AN: 67946

Other (OTH) AF: 0.434 AC: 914 AN: 2108

Alfa AF: 0.460 Hom.: 23591

Bravo AF: 0.483

Asia WGS AF: 0.669 AC: 2330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.23
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs7204439; hg19: chr16-661335;