rs329017

Positions:

• chr18-9492198-T-C

Variant summary

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

The NM_006788.4(RALBP1):​c.-56+16507T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,036 control chromosomes in the GnomAD database, including 8,707 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 0.33 (8707 hom., cov: 31)
• Consequence: RALBP1 NM_006788.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALBP1	NM_006788.4	c.-56+16507T>C		intron_variant		ENST00000383432.8	NP_006779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALBP1	ENST00000383432.8	c.-56+16507T>C		intron_variant		1	NM_006788.4	ENSP00000372924.3

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49788 AN: 151918 Hom.: 8700 Cov.: 31

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.355

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.328 AC: 49816 AN: 152036 Hom.: 8707 Cov.: 31 AF XY: 0.328 AC XY: 24409 AN XY: 74320

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.0816

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.355

Alfa AF: 0.360 Hom.: 13899

Bravo AF: 0.319

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.7
DANN	Benign	0.42

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: rs329017; hg19: chr18-9492196;