rs28729663

Variant names:

• chr22-50780578-G-A
• rs28729663
• NM_001130919.3:c.107+1610C>T

Variant summary

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

The NM_001130919.3(RABL2B):​c.107+1610C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 418,198 control chromosomes in the GnomAD database, including 6,837 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 0.20 (3570 hom., cov: 29)
  • Exomes 𝑓: 0.15 (3267 hom.)
• Consequence: RABL2B NM_001130919.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• Publications: 5 publications found

Genes affected

RABL2B (HGNC:9800): (RAB, member of RAS oncogene family like 2B) The RABL2B protein is a member of the RAB gene family which belongs to the RAS GTPase superfamily. RABL2B is located within a subtelomeric region of 22q13.3. Multiple alternatively spliced transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ENSG00000291064 (HGNC:):

RPL23AP82 (HGNC:33730): (ribosomal protein L23a pseudogene 82)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130919.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABL2B	NM_001130919.3	MANE Select	c.107+1610C>T		intron	N/A	NP_001124391.1
	RABL2B	NM_001350008.2		c.107+1610C>T		intron	N/A	NP_001336937.1
	RABL2B	NM_001350009.2		c.107+1610C>T		intron	N/A	NP_001336938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RABL2B	ENST00000691320.1	MANE Select	c.107+1610C>T		intron	N/A	ENSP00000509250.1
	RABL2B	ENST00000395593.7	TSL:1	c.107+1610C>T		intron	N/A	ENSP00000378958.3
	RABL2B	ENST00000354869.8	TSL:1	c.107+1610C>T		intron	N/A	ENSP00000346940.3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30623 AN: 151586 Hom.: 3553 Cov.: 29

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.148 AC: 39402 AN: 266494 Hom.: 3267 Cov.: 0 AF XY: 0.147 AC XY: 21931 AN XY: 149104

African (AFR) AF: 0.320 AC: 2129 AN: 6662

American (AMR) AF: 0.189 AC: 3535 AN: 18724

Ashkenazi Jewish (ASJ) AF: 0.0837 AC: 650 AN: 7770

East Asian (EAS) AF: 0.121 AC: 1038 AN: 8578

South Asian (SAS) AF: 0.150 AC: 7661 AN: 50968

European-Finnish (FIN) AF: 0.176 AC: 4488 AN: 25450

Middle Eastern (MID) AF: 0.110 AC: 279 AN: 2540

European-Non Finnish (NFE) AF: 0.133 AC: 17796 AN: 133694

Other (OTH) AF: 0.151 AC: 1826 AN: 12108

GnomAD4 genome AF: 0.202 AC: 30684 AN: 151704 Hom.: 3570 Cov.: 29 AF XY: 0.205 AC XY: 15231 AN XY: 74142

African (AFR) AF: 0.334 AC: 13785 AN: 41280

American (AMR) AF: 0.205 AC: 3120 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 339 AN: 3464

East Asian (EAS) AF: 0.121 AC: 627 AN: 5164

South Asian (SAS) AF: 0.166 AC: 799 AN: 4810

European-Finnish (FIN) AF: 0.189 AC: 1989 AN: 10530

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.139 AC: 9456 AN: 67908

Other (OTH) AF: 0.199 AC: 419 AN: 2102

Alfa AF: 0.185 Hom.: 457

Bravo AF: 0.207

Asia WGS AF: 0.224 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.95
DANN	Benign	0.41
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28729663; hg19: chr22-51219006; COSMIC: COSV61483247; COSMIC: COSV61483247;