chr20-3865997-C-T

Variant names:

• chr20-3865997-C-T
• rs61739401
• NM_020746.5:c.1473C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020746.5(MAVS):​c.1473C>T​(p.Gly491Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,612,844 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (21 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (11 hom.)
• Consequence: MAVS NM_020746.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.14
• Publications: 2 publications found

Genes affected

MAVS (HGNC:29233): (mitochondrial antiviral signaling protein) This gene encodes an intermediary protein necessary in the virus-triggered beta interferon signaling pathways. It is required for activation of transcription factors which regulate expression of beta interferon and contributes to antiviral innate immunity. [provided by RefSeq, Jul 2020]

PANK2-AS1 (HGNC:40732): (PANK2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 20-3865997-C-T is Benign according to our data. Variant chr20-3865997-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 782664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.14 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00873 (1330/152272) while in subpopulation AFR AF = 0.0303 (1258/41554). AF 95% confidence interval is 0.0289. There are 21 homozygotes in GnomAd4. There are 616 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1330 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020746.5. 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
	MAVS	NM_020746.5	MANE Select	c.1473C>T	p.Gly491Gly	synonymous	Exon 7 of 7	NP_065797.2	Q7Z434-1
	MAVS	NM_001206491.2		c.1050C>T	p.Gly350Gly	synonymous	Exon 6 of 6	NP_001193420.1	Q7Z434-4
	MAVS	NM_001385663.1		c.1050C>T	p.Gly350Gly	synonymous	Exon 8 of 8	NP_001372592.1	Q7Z434-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAVS	ENST00000428216.4	TSL:1 MANE Select	c.1473C>T	p.Gly491Gly	synonymous	Exon 7 of 7	ENSP00000401980.2	Q7Z434-1
	MAVS	ENST00000416600.6	TSL:1	c.1050C>T	p.Gly350Gly	synonymous	Exon 6 of 6	ENSP00000413749.2	Q7Z434-4
	MAVS	ENST00000883971.1		c.1503C>T	p.Gly501Gly	synonymous	Exon 6 of 6	ENSP00000554030.1

Frequencies

GnomAD3 genomes AF: 0.00873 AC: 1329 AN: 152154 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00909

GnomAD2 exomes AF: 0.00206 AC: 509 AN: 247310 AF XY: 0.00140

Gnomad AFR exome AF: 0.0294

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000539

Gnomad OTH exome AF: 0.000827

GnomAD4 exome AF: 0.000892 AC: 1303 AN: 1460572 Hom.: 11 Cov.: 32 AF XY: 0.000778 AC XY: 565 AN XY: 726632

African (AFR) AF: 0.0325 AC: 1088 AN: 33480

American (AMR) AF: 0.00134 AC: 60 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52170

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5764

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111976

Other (OTH) AF: 0.00169 AC: 102 AN: 60382

GnomAD4 genome AF: 0.00873 AC: 1330 AN: 152272 Hom.: 21 Cov.: 33 AF XY: 0.00827 AC XY: 616 AN XY: 74442

African (AFR) AF: 0.0303 AC: 1258 AN: 41554

American (AMR) AF: 0.00294 AC: 45 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68004

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.00233 Hom.: 3

Bravo AF: 0.00995

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	3.7
DANN	Benign	0.33
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs61739401; hg19: chr20-3846644;