12-55985643-G-C

Variant names:

• chr12-55985643-G-C
• rs1873914
• NM_002868.4:c.-92-1226G>C

Variant summary

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

The NM_002868.4(RAB5B):​c.-92-1226G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 453,960 control chromosomes in the GnomAD database, including 27,519 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 0.31 (8291 hom., cov: 32)
  • Exomes 𝑓: 0.35 (19228 hom.)
• Consequence: RAB5B NM_002868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 46 publications found

Genes affected

RAB5B (HGNC:9784): (RAB5B, member RAS oncogene family) Enables GDP binding activity; GTP-dependent protein binding activity; and GTPase activity. Involved in antigen processing and presentation and plasma membrane to endosome transport. Located in endosome and extracellular exosome. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002868.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB5B	NM_002868.4	MANE Select	c.-92-1226G>C		intron	N/A	NP_002859.1	P61020-1
	RAB5B	NM_001414458.1		c.152-1226G>C		intron	N/A	NP_001401387.1
	RAB5B	NM_001252036.2		c.-92-1226G>C		intron	N/A	NP_001238965.1	P61020-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB5B	ENST00000360299.10	TSL:1 MANE Select	c.-92-1226G>C		intron	N/A	ENSP00000353444.5	P61020-1
	RAB5B	ENST00000553116.5	TSL:1	c.-92-1226G>C		intron	N/A	ENSP00000450168.1	P61020-1
	RAB5B	ENST00000549505.5	TSL:1	n.-92-1226G>C		intron	N/A	ENSP00000450285.1	F8VPW9

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47674 AN: 151964 Hom.: 8291 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.348 AC: 104935 AN: 301878 Hom.: 19228 Cov.: 0 AF XY: 0.342 AC XY: 58829 AN XY: 171988

African (AFR) AF: 0.171 AC: 1459 AN: 8556

American (AMR) AF: 0.267 AC: 7225 AN: 27020

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 4009 AN: 10744

East Asian (EAS) AF: 0.226 AC: 2062 AN: 9128

South Asian (SAS) AF: 0.276 AC: 16368 AN: 59378

European-Finnish (FIN) AF: 0.379 AC: 4662 AN: 12314

Middle Eastern (MID) AF: 0.240 AC: 664 AN: 2764

European-Non Finnish (NFE) AF: 0.402 AC: 63495 AN: 157854

Other (OTH) AF: 0.353 AC: 4991 AN: 14120

GnomAD4 genome AF: 0.314 AC: 47687 AN: 152082 Hom.: 8291 Cov.: 32 AF XY: 0.310 AC XY: 23042 AN XY: 74354

African (AFR) AF: 0.169 AC: 7005 AN: 41484

American (AMR) AF: 0.290 AC: 4425 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1359 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1194 AN: 5182

South Asian (SAS) AF: 0.269 AC: 1297 AN: 4816

European-Finnish (FIN) AF: 0.363 AC: 3836 AN: 10574

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27257 AN: 67966

Other (OTH) AF: 0.320 AC: 676 AN: 2112

Alfa AF: 0.353 Hom.: 1235

Bravo AF: 0.305

Asia WGS AF: 0.205 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.8
DANN	Benign	0.88
PhyloP100		0.36
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: rs1873914; hg19: chr12-56379427;