1-230979199-T-C

Position:

• chr1-230979199-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_022786.3(ARV1):​c.94T>C​(p.Tyr32His) variant causes a missense change. The variant allele was found at a frequency of 0.00171 in 1,613,546 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0090 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (24 hom.)
• Consequence: ARV1 NM_022786.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.65

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009450704).
• BP6: Variant 1-230979199-T-C is Benign according to our data. Variant chr1-230979199-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 445383.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00897 (1366/152228) while in subpopulation AFR AF= 0.0311 (1293/41538). AF 95% confidence interval is 0.0297. There are 20 homozygotes in gnomad4. There are 646 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARV1	NM_022786.3	c.94T>C	p.Tyr32His	missense_variant	1/6	ENST00000310256.7	NP_073623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARV1	ENST00000310256.7	c.94T>C	p.Tyr32His	missense_variant	1/6	1	NM_022786.3	ENSP00000312458	P1

Frequencies

GnomAD3 genomes AF: 0.00896 AC: 1363 AN: 152110 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00237 AC: 594 AN: 250618 Hom.: 11 AF XY: 0.00176 AC XY: 239 AN XY: 135510

Gnomad AFR exome AF: 0.0314

Gnomad AMR exome AF: 0.00157

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.000821

GnomAD4 exome AF: 0.000951 AC: 1389 AN: 1461318 Hom.: 24 Cov.: 31 AF XY: 0.000825 AC XY: 600 AN XY: 726982

Gnomad4 AFR exome AF: 0.0328

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000872

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00897 AC: 1366 AN: 152228 Hom.: 20 Cov.: 32 AF XY: 0.00868 AC XY: 646 AN XY: 74424

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00154 Hom.: 5

Bravo AF: 0.0100

ESP6500AA AF: 0.0275 AC: 121

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00275 AC: 334

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000238

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 22, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T;T
MetaRNN	Benign	0.0095	T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.028	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.82
MVP		0.93
MPC		0.56
ClinPred		0.019	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34745784; hg19: chr1-231114945;