2-200896179-G-C

Variant names:

• chr2-200896179-G-C
• rs13421776
• NM_001369441.2:c.726+789G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369441.2(NIF3L1):​c.726+789G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,946 control chromosomes in the GnomAD database, including 4,705 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4705 hom., cov: 31)
• Consequence: NIF3L1 NM_001369441.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369441.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIF3L1	NM_001369441.2	MANE Select	c.726+789G>C		intron	N/A	NP_001356370.1
	NIF3L1	NM_001136039.2		c.726+789G>C		intron	N/A	NP_001129511.1
	NIF3L1	NM_001369442.1		c.726+789G>C		intron	N/A	NP_001356371.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIF3L1	ENST00000409020.6	TSL:5 MANE Select	c.726+789G>C		intron	N/A	ENSP00000386394.1
	NIF3L1	ENST00000359683.8	TSL:1	c.645+789G>C		intron	N/A	ENSP00000352711.4
	NIF3L1	ENST00000409588.1	TSL:1	c.726+789G>C		intron	N/A	ENSP00000387021.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34526 AN: 151828 Hom.: 4697 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.00868

Gnomad SAS AF: 0.0808

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.228 AC: 34576 AN: 151946 Hom.: 4705 Cov.: 31 AF XY: 0.223 AC XY: 16561 AN XY: 74286

African (AFR) AF: 0.376 AC: 15540 AN: 41382

American (AMR) AF: 0.169 AC: 2579 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3472

East Asian (EAS) AF: 0.00870 AC: 45 AN: 5172

South Asian (SAS) AF: 0.0809 AC: 390 AN: 4822

European-Finnish (FIN) AF: 0.182 AC: 1926 AN: 10554

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12603 AN: 67950

Other (OTH) AF: 0.219 AC: 461 AN: 2106

Alfa AF: 0.217 Hom.: 525

Bravo AF: 0.236

Asia WGS AF: 0.0730 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

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: rs13421776; hg19: chr2-201760902;