chr12-68686813-G-C

Position:

• chr12-68686813-G-C

Variant summary

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

The ENST00000433116.2(NUP107-DT):​n.25C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 507,396 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (12 hom., cov: 33)
  • Exomes 𝑓: 0.012 (38 hom.)
• Consequence: NUP107-DT ENST00000433116.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.837

Genes affected

NUP107-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-68686813-G-C is Benign according to our data. Variant chr12-68686813-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1198391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00961 (1464/152334) while in subpopulation SAS AF= 0.0209 (101/4832). AF 95% confidence interval is 0.0176. There are 12 homozygotes in gnomad4. There are 695 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100507250	NR_038930.1	n.47C>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP107-DT	ENST00000502102.2	n.822+121C>G		intron_variant		1
NUP107-DT	ENST00000433116.2	n.25C>G		non_coding_transcript_exon_variant	1/2	2
NUP107-DT	ENST00000500695.2	n.47C>G		non_coding_transcript_exon_variant	1/3	5
NUP107-DT	ENST00000690517.1	n.64C>G		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes AF: 0.00961 AC: 1463 AN: 152216 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00994

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.00955

GnomAD4 exome AF: 0.0124 AC: 4407 AN: 355062 Hom.: 38 Cov.: 3 AF XY: 0.0132 AC XY: 2444 AN XY: 185702

Gnomad4 AFR exome AF: 0.00186

Gnomad4 AMR exome AF: 0.00866

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0202

Gnomad4 FIN exome AF: 0.00489

Gnomad4 NFE exome AF: 0.0140

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.00961 AC: 1464 AN: 152334 Hom.: 12 Cov.: 33 AF XY: 0.00933 AC XY: 695 AN XY: 74480

Gnomad4 AFR AF: 0.00243

Gnomad4 AMR AF: 0.00993

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.00640

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.00382 Hom.: 0

Bravo AF: 0.00966

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 22, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.45

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: rs149838156; hg19: chr12-69080593;