rs28729663

chr22-50780578-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

RPL23AP7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABL2B	NM_001130919.3	c.107+1610C>T		intron_variant		ENST00000691320.1
RPL23AP82	NR_026981.1	n.242-2542G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABL2B	ENST00000691320.1	c.107+1610C>T		intron_variant			NM_001130919.3	A2
RPL23AP7	ENST00000496652.5	n.380-2542G>A		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.0837

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.151

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

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0979

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.199

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.95
Dann	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs28729663; hg19: chr22-51219006; COSMIC: COSV61483247; COSMIC: COSV61483247;