rs4982303

Positions:

• chr14-35660765-A-C

Variant summary

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

The NM_001346249.2(RALGAPA1):​c.5329-1569T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,030 control chromosomes in the GnomAD database, including 7,382 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 0.26 (7382 hom., cov: 32)
• Consequence: RALGAPA1 NM_001346249.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

Genes affected

RALGAPA1 (HGNC:17770): (Ral GTPase activating protein catalytic subunit alpha 1) This gene encodes a major subunit of the RAL-GTPase activating protein. A similar protein in mouse binds E12, a transcriptional regulator of immunoglobulin genes. The mouse protein also functions in skeletal muscle by binding to the regulatory 14-3-3 proteins upon stimulation with insulin or muscle contraction. A pseudogene of this gene has been identified on chromosome 9. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGAPA1	NM_001346249.2	c.5329-1569T>G		intron_variant		ENST00000680220.1	NP_001333178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGAPA1	ENST00000680220.1	c.5329-1569T>G		intron_variant			NM_001346249.2	ENSP00000506280

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39343 AN: 151910 Hom.: 7341 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.259 AC: 39438 AN: 152030 Hom.: 7382 Cov.: 32 AF XY: 0.261 AC XY: 19400 AN XY: 74338

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.231

Alfa AF: 0.211 Hom.: 738

Bravo AF: 0.267

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.65

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: rs4982303; hg19: chr14-36129971;