19-57456271-TAA-T

Variant names:

• chr19-57456271-TAA-T
• rs200574657
• NM_020633.4:c.214_215delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_020633.4(VN1R1):​c.214_215delTT​(p.Leu72AsnfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,613,594 control chromosomes in the GnomAD database, including 42 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (27 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (15 hom.)
• Consequence: VN1R1 NM_020633.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.534

Genes affected

VN1R1 (HGNC:13548): (vomeronasal 1 receptor 1) Pheromones are chemical signals that elicit specific behavioral responses and physiologic alterations in recipients of the same species. The protein encoded by this gene is similar to pheromone receptors and is primarily localized to the olfactory mucosa. An alternate splice variant of this gene is thought to exist, but its full length nature has not been determined. [provided by RefSeq, Jul 2008]

ENSG00000268163 (HGNC:):

ACMG classification

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

• BP6: Variant 19-57456271-TAA-T is Benign according to our data. Variant chr19-57456271-TAA-T is described in ClinVar as [Benign]. Clinvar id is 712016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00947 (1442/152256) while in subpopulation AFR AF = 0.0327 (1359/41538). AF 95% confidence interval is 0.0313. There are 27 homozygotes in GnomAd4. There are 683 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VN1R1	NM_020633.4	c.214_215delTT	p.Leu72AsnfsTer22	frameshift_variant	Exon 1 of 1	ENST00000321039.5	NP_065684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VN1R1	ENST00000321039.5	c.214_215delTT	p.Leu72AsnfsTer22	frameshift_variant	Exon 1 of 1	6	NM_020633.4	ENSP00000322339.3
ENSG00000268163	ENST00000596831.1	c.200-91_200-90delTT		intron_variant	Intron 3 of 5	2		ENSP00000470969.1
ENSG00000268163	ENST00000415705.3	n.300-91_300-90delTT		intron_variant	Intron 2 of 3	2
ENSG00000268163	ENST00000601945.1	n.-34_-33delTT		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.00946 AC: 1439 AN: 152140 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.00259 AC: 650 AN: 250884 AF XY: 0.00183

Gnomad AFR exome AF: 0.0331

Gnomad AMR exome AF: 0.00209

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000256

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.000987 AC: 1443 AN: 1461338 Hom.: 15 AF XY: 0.000872 AC XY: 634 AN XY: 726942

Gnomad4 AFR exome AF: 0.0307 AC: 1024 AN: 33398

Gnomad4 AMR exome AF: 0.00258 AC: 115 AN: 44630

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26118

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39688

Gnomad4 SAS exome AF: 0.0000232 AC: 2 AN: 86188

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53416

Gnomad4 NFE exome AF: 0.000159 AC: 177 AN: 1111766

Gnomad4 Remaining exome AF: 0.00179 AC: 108 AN: 60368

GnomAD4 genome AF: 0.00947 AC: 1442 AN: 152256 Hom.: 27 Cov.: 32 AF XY: 0.00917 AC XY: 683 AN XY: 74452

Gnomad4 AFR AF: 0.0327 AC: 0.032717 AN: 0.032717

Gnomad4 AMR AF: 0.00373 AC: 0.0037289 AN: 0.0037289

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207125 AN: 0.000207125

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000147 AC: 0.000147029 AN: 0.000147029

Gnomad4 OTH AF: 0.00710 AC: 0.00709555 AN: 0.00709555

Alfa AF: 0.00515 Hom.: 3

Bravo AF: 0.0110

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=192/8	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

Publications

LitVar

Other links and lift over

dbSNP: rs200574657; hg19: chr19-57967639;