rs329017

Variant names:

• chr18-9492198-T-C
• rs329017
• NM_006788.4:c.-56+16507T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006788.4. 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
	RALBP1	NM_006788.4	MANE Select	c.-56+16507T>C		intron	N/A	NP_006779.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALBP1	ENST00000383432.8	TSL:1 MANE Select	c.-56+16507T>C		intron	N/A	ENSP00000372924.3
	RALBP1	ENST00000019317.8	TSL:1	c.-56+17022T>C		intron	N/A	ENSP00000019317.4
	RALBP1	ENST00000609094.2	TSL:2	c.-56+16507T>C		intron	N/A	ENSP00000492511.1

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

African (AFR) AF: 0.250 AC: 10380 AN: 41480

American (AMR) AF: 0.348 AC: 5312 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1323 AN: 3466

East Asian (EAS) AF: 0.0816 AC: 423 AN: 5184

South Asian (SAS) AF: 0.169 AC: 813 AN: 4820

European-Finnish (FIN) AF: 0.469 AC: 4943 AN: 10550

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25592 AN: 67940

Other (OTH) AF: 0.355 AC: 750 AN: 2112

Alfa AF: 0.353 Hom.: 30053

Bravo AF: 0.319

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.7
DANN	Benign	0.42
PhyloP100		0.27
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: rs329017; hg19: chr18-9492196;