chr1-230979114-C-T

Variant names:

• chr1-230979114-C-T
• rs368096556
• NM_022786.3:c.9C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS1

The NM_022786.3(ARV1):​c.9C>T​(p.Asn3Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,426,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: ARV1 NM_022786.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.535
• Publications: 0 publications found

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]

TTC13 (HGNC:26204): (tetratricopeptide repeat domain 13)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 1-230979114-C-T is Benign according to our data. Variant chr1-230979114-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3053876.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.535 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000266 (38/1426832) while in subpopulation AMR AF = 0.000825 (35/42414). AF 95% confidence interval is 0.000609. There are 0 homozygotes in GnomAdExome4. There are 19 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022786.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARV1	NM_022786.3	MANE Select	c.9C>T	p.Asn3Asn	synonymous	Exon 1 of 6	NP_073623.1	Q9H2C2
	ARV1	NM_001346992.2		c.9C>T	p.Asn3Asn	synonymous	Exon 1 of 7	NP_001333921.1
	ARV1	NR_144538.2		n.21C>T		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARV1	ENST00000310256.7	TSL:1 MANE Select	c.9C>T	p.Asn3Asn	synonymous	Exon 1 of 6	ENSP00000312458.2	Q9H2C2
	ARV1	ENST00000893839.1		c.9C>T	p.Asn3Asn	synonymous	Exon 1 of 7	ENSP00000563898.1
	ARV1	ENST00000893842.1		c.9C>T	p.Asn3Asn	synonymous	Exon 1 of 6	ENSP00000563901.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000144 AC: 30 AN: 208406 AF XY: 0.000107

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000890

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000195

GnomAD4 exome AF: 0.0000266 AC: 38 AN: 1426832 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 19 AN XY: 707080

African (AFR) AF: 0.00 AC: 0 AN: 33034

American (AMR) AF: 0.000825 AC: 35 AN: 42414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39206

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097332

Other (OTH) AF: 0.0000169 AC: 1 AN: 59090

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000435 Hom.: 0

Bravo AF: 0.0000453

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ARV1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.8
DANN	Benign	0.90
PhyloP100		-0.54
PromoterAI		0.44	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs368096556; hg19: chr1-231114860; COSMIC: COSV59617211; COSMIC: COSV59617211;