Genetic Variant RAB40C:c.342+171T>C (chr16-625680-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021168.5(RAB40C):c.342+171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 844,800 control chromosomes in the GnomAD database, including 94,700 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 0.47 ( 17523 hom., cov: 35)

Exomes 𝑓: 0.46 ( 77177 hom. )

Consequence

RAB40C
NM_021168.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Variant links:

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]

RAB40C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB40C	NM_021168.5 link	c.342+171T>C		intron_variant	Intron 4 of 5	ENST00000248139.8	NP_066991.3	Q96S21-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB40C	ENST00000248139.8 link	c.342+171T>C		intron_variant	Intron 4 of 5	1	NM_021168.5	ENSP00000248139.3		Q96S21-1

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

72000

AN:

152052

Hom.:

17482

Cov.:

show subpopulations

Gnomad AFR

AF:

0.519

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.420

GnomAD4 exome

AF:

0.462

AC:

319701

AN:

692630

Hom.:

77177

Cov.:

AF XY:

0.468

AC XY:

166047

AN XY:

355154

show subpopulations

Gnomad4 AFR exome

AF:

0.519

Gnomad4 AMR exome

AF:

0.537

Gnomad4 ASJ exome

AF:

0.385

Gnomad4 EAS exome

AF:

0.695

Gnomad4 SAS exome

AF:

0.618

Gnomad4 FIN exome

AF:

0.519

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.447

GnomAD4 genome

AF:

0.474

AC:

72096

AN:

152170

Hom.:

17523

Cov.:

AF XY:

0.481

AC XY:

35805

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.487

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.654

Gnomad4 SAS

AF:

0.621

Gnomad4 FIN

AF:

0.510

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.431

Hom.:

9782

Bravo

AF:

0.467

Asia WGS

AF:

0.669

AC:

2329

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.22

DANN

Benign

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over