rs7917

Positions:

• chr2-200903515-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001369441.2(NIF3L1):​c.971C>T​(p.Thr324Ile) variant causes a missense change. The variant allele was found at a frequency of 0.227 in 1,611,958 control chromosomes in the GnomAD database, including 48,633 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.31 (9944 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38689 hom.)
• Consequence: NIF3L1 NM_001369441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.91

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4081597E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIF3L1	NM_001369441.2	c.971C>T	p.Thr324Ile	missense_variant	7/7	ENST00000409020.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIF3L1	ENST00000409020.6	c.971C>T	p.Thr324Ile	missense_variant	7/7	5	NM_001369441.2	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47812 AN: 151950 Hom.: 9920 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.284

GnomAD3 exomes AF: 0.214 AC: 53455 AN: 249492 Hom.: 7621 AF XY: 0.211 AC XY: 28524 AN XY: 135362

Gnomad AFR exome AF: 0.607

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.00801

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.211

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.218 AC: 318064 AN: 1459890 Hom.: 38689 Cov.: 32 AF XY: 0.216 AC XY: 157064 AN XY: 726264

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.00507

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.218

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.315 AC: 47891 AN: 152068 Hom.: 9944 Cov.: 32 AF XY: 0.310 AC XY: 23022 AN XY: 74360

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.0125

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.290

Alfa AF: 0.241 Hom.: 8478

Bravo AF: 0.326

TwinsUK AF: 0.214 AC: 793

ALSPAC AF: 0.218 AC: 841

ESP6500AA AF: 0.579 AC: 2196

ESP6500EA AF: 0.221 AC: 1824

ExAC AF: 0.222 AC: 26806

Asia WGS AF: 0.140 AC: 488 AN: 3478

EpiCase AF: 0.220

EpiControl AF: 0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.037
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.86
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.00014	T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P;P;P;P;P
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.14
Sift	Benign	0.82	T
Sift4G	Benign	0.65	T
Vest4		0.10
ClinPred		0.036	T
GERP RS		5.3

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: rs7917; hg19: chr2-201768238; COSMIC: COSV62900214; COSMIC: COSV62900214;