8-131969174-C-T

Variant names:

• chr8-131969174-C-T
• rs10505583
• NM_015137.6:c.991+744C>T

Variant summary

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

The NM_015137.6(EFR3A):​c.991+744C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,032 control chromosomes in the GnomAD database, including 1,241 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 0.12 (1241 hom., cov: 32)
• Consequence: EFR3A NM_015137.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

Genes affected

EFR3A (HGNC:28970): (EFR3 homolog A) The protein encoded by this gene is part of a complex that plays a role in maintaining an active pool of phosphatidylinositol 4-kinase (PI4K) at the plasma membrane. This protein is thought to be a peripheral membrane protein that associates with the plasma membrane through palmitoylation. Studies indicate that this gene product plays a role in controlling G protein-coupled receptor (GPCR) activity by affecting receptor phosphorylation. Whole exome sequencing studies have implicated mutations in this gene with autism spectrum disorders. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EFR3A	NM_015137.6	c.991+744C>T		intron_variant	Intron 9 of 22	ENST00000254624.10	NP_055952.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EFR3A	ENST00000254624.10	c.991+744C>T		intron_variant	Intron 9 of 22	1	NM_015137.6	ENSP00000254624.5
EFR3A	ENST00000519656.1	c.883+744C>T		intron_variant	Intron 9 of 22	1		ENSP00000428086.1
EFR3A	ENST00000637848.1	c.1072+744C>T		intron_variant	Intron 9 of 22	5		ENSP00000490312.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18480 AN: 151914 Hom.: 1239 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.122 AC: 18499 AN: 152032 Hom.: 1241 Cov.: 32 AF XY: 0.122 AC XY: 9084 AN XY: 74300

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0916

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0377 Hom.: 48

Bravo AF: 0.120

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.070
DANN	Benign	0.41

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: rs10505583; hg19: chr8-132981421;