2-200891952-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000359683.8(NIF3L1):c.-56-17A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000674 in 1,604,236 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (1 hom.)
• Consequence: NIF3L1 ENST00000359683.8 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700

Genes affected

NIF3L1 (HGNC:13390): (NGG1 interacting factor 3 like 1) Enables identical protein binding activity. Involved in positive regulation of transcription, DNA-templated. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 2-200891952-A-G is Benign according to our data. Variant chr2-200891952-A-G is described in ClinVar as [Benign]. Clinvar id is 720553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIF3L1	NM_001369441.2	c.9A>G	p.Ser3=	synonymous_variant	2/7	ENST00000409020.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIF3L1	ENST00000409020.6	c.9A>G	p.Ser3=	synonymous_variant	2/7	5	NM_001369441.2	P1

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 535 AN: 152140 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

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: 0.0000882

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000862 AC: 205 AN: 237744 Hom.: 1 AF XY: 0.000612 AC XY: 79 AN XY: 129052

Gnomad AFR exome AF: 0.0117

Gnomad AMR exome AF: 0.000487

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000112

Gnomad OTH exome AF: 0.000520

GnomAD4 exome AF: 0.000375 AC: 545 AN: 1451978 Hom.: 1 Cov.: 30 AF XY: 0.000324 AC XY: 234 AN XY: 721398

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.000534

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000732

Gnomad4 OTH exome AF: 0.000833

GnomAD4 genome AF: 0.00352 AC: 536 AN: 152258 Hom.: 4 Cov.: 32 AF XY: 0.00342 AC XY: 255 AN XY: 74458

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00173 Hom.: 0

Bravo AF: 0.00388

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	6.5
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs115524838; hg19: chr2-201756675; COSMIC: COSV53768598; COSMIC: COSV53768598;