chr16-611335-T-C

Position:

• chr16-611335-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000248139.8(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 ENST00000248139.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RAB40C	NM_021168.5	c.143-5873T>C		intron_variant		ENST00000248139.8	NP_066991.3
LOC124903618	XR_007064934.1	n.4930A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB40C	ENST00000248139.8	c.143-5873T>C		intron_variant		1	NM_021168.5	ENSP00000248139	P1

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

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.434

Alfa AF: 0.476 Hom.: 2258

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs7204439; hg19: chr16-661335;