14-35627049-G-GA

Position:

• chr14-35627049-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001346249.2(RALGAPA1):​c.6857+40dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (62260 hom., cov: 0)
  • Exomes 𝑓: 0.51 (15623 hom.)
  • Failed GnomAD Quality Control
• Consequence: RALGAPA1 NM_001346249.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.646

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 -10 ACMG points.

• BP6: Variant 14-35627049-G-GA is Benign according to our data. Variant chr14-35627049-G-GA is described in ClinVar as [Benign]. Clinvar id is 1327933.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGAPA1	NM_001346249.2	c.6857+40dupT		intron_variant		ENST00000680220.1	NP_001333178.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGAPA1	ENST00000680220.1	c.6857+40_6857+41insT		intron_variant			NM_001346249.2	ENSP00000506280.1

Frequencies

GnomAD3 genomes AF: 0.970 AC: 128327 AN: 132348 Hom.: 62262 Cov.: 0

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.965

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.971

GnomAD3 exomes AF: 0.509 AC: 46803 AN: 91952 Hom.: 2405 AF XY: 0.507 AC XY: 24983 AN XY: 49230

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.513

Gnomad ASJ exome AF: 0.500

Gnomad EAS exome AF: 0.499

Gnomad SAS exome AF: 0.495

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.509

Gnomad OTH exome AF: 0.507

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.508 AC: 507389 AN: 997862 Hom.: 15623 Cov.: 24 AF XY: 0.508 AC XY: 246565 AN XY: 485652

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.499

Gnomad4 ASJ exome AF: 0.503

Gnomad4 EAS exome AF: 0.484

Gnomad4 SAS exome AF: 0.496

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.505

GnomAD4 genome AF: 0.970 AC: 128321 AN: 132340 Hom.: 62260 Cov.: 0 AF XY: 0.968 AC XY: 61032 AN XY: 63038

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.982

Gnomad4 ASJ AF: 0.991

Gnomad4 EAS AF: 0.874

Gnomad4 SAS AF: 0.965

Gnomad4 FIN AF: 0.985

Gnomad4 NFE AF: 0.986

Gnomad4 OTH AF: 0.972

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs34349314; hg19: chr14-36096255;