1-230988309-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022786.3(ARV1):c.175-11T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,577,898 control chromosomes in the GnomAD database, including 92,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (8842 hom., cov: 32)
  • Exomes 𝑓: 0.33 (83450 hom.)
• Consequence: ARV1 NM_022786.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0009114
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0200

Genes affected

ARV1 (HGNC:29561): (ARV1 homolog, fatty acid homeostasis modulator) this gene encodes a transmembrane protein that contains a conserved zinc ribbon motif at the N- terminus. A similar protein in mouse is thought to function in fatty acid homeostasis. Mutations in this gene are associated with early infantile epileptic encephalopathy 38. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 1-230988309-T-C is Benign according to our data. Variant chr1-230988309-T-C is described in ClinVar as [Benign]. Clinvar id is 1192479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARV1	NM_022786.3	c.175-11T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000310256.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARV1	ENST00000310256.7	c.175-11T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_022786.3	P1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51021 AN: 151944 Hom.: 8837 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.362

GnomAD3 exomes AF: 0.351 AC: 85074 AN: 242140 Hom.: 16211 AF XY: 0.364 AC XY: 47632 AN XY: 130804

Gnomad AFR exome AF: 0.329

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.444

Gnomad EAS exome AF: 0.543

Gnomad SAS exome AF: 0.501

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.335 AC: 477317 AN: 1425836 Hom.: 83450 Cov.: 30 AF XY: 0.342 AC XY: 242902 AN XY: 710280

Gnomad4 AFR exome AF: 0.337

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.501

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.320

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.336 AC: 51045 AN: 152062 Hom.: 8842 Cov.: 32 AF XY: 0.337 AC XY: 25047 AN XY: 74356

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.361

Alfa AF: 0.339 Hom.: 1717

Bravo AF: 0.334

Asia WGS AF: 0.456 AC: 1575 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 38 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	11
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00091
dbscSNV1_RF	Benign	0.078
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: rs10779804; hg19: chr1-231124055; COSMIC: COSV59617270;