rs329007

chr18-9522608-G-Achr18-9522608-G-C

Variant summary

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

The NM_006788.4(RALBP1):c.1053+99G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 966,870 control chromosomes in the GnomAD database, including 280,615 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 0.78 (47211 hom., cov: 33)
  • Exomes 𝑓: 0.75 (233404 hom.)
• Consequence: RALBP1 NM_006788.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

Genes affected

RALBP1 (HGNC:9841): (ralA binding protein 1) RALBP1 plays a role in receptor-mediated endocytosis and is a downstream effector of the small GTP-binding protein RAL (see RALA; MIM 179550). Small G proteins, such as RAL, have GDP-bound inactive and GTP-bound active forms, which shift from the inactive to the active state through the action of RALGDS (MIM 601619), which in turn is activated by RAS (see HRAS; MIM 190020) (summary by Feig, 2003 [PubMed 12888294]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RALBP1	NM_006788.4	c.1053+99G>A		intron_variant		ENST00000383432.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RALBP1	ENST00000383432.8	c.1053+99G>A		intron_variant		1	NM_006788.4	P1
RALBP1	ENST00000019317.8	c.1053+99G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119331 AN: 152132 Hom.: 47168 Cov.: 33

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 0.754 AC: 613927 AN: 814618 Hom.: 233404 AF XY: 0.748 AC XY: 310059 AN XY: 414336

Gnomad4 AFR exome AF: 0.848

Gnomad4 AMR exome AF: 0.721

Gnomad4 ASJ exome AF: 0.791

Gnomad4 EAS exome AF: 0.578

Gnomad4 SAS exome AF: 0.612

Gnomad4 FIN exome AF: 0.857

Gnomad4 NFE exome AF: 0.767

Gnomad4 OTH exome AF: 0.761

GnomAD4 genome AF: 0.784 AC: 119434 AN: 152252 Hom.: 47211 Cov.: 33 AF XY: 0.782 AC XY: 58226 AN XY: 74432

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.796

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.776

Alfa AF: 0.772 Hom.: 62835

Bravo AF: 0.780

Asia WGS AF: 0.566 AC: 1970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.75
Dann	Benign	0.62

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: rs329007; hg19: chr18-9522606;