2-200891952-A-G

Variant names:

• chr2-200891952-A-G
• rs115524838
• NM_001369441.2:c.9A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001369441.2(NIF3L1):​c.9A>G​(p.Ser3Ser) variant causes a synonymous 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (1 hom.)
• Consequence: NIF3L1 NM_001369441.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00700
• Publications: 2 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 -17 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/Likely_benign. ClinVar VariationId is 720553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.007 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIF3L1	NM_001369441.2	MANE Select	c.9A>G	p.Ser3Ser	synonymous	Exon 2 of 7	NP_001356370.1	Q9GZT8-1
	NIF3L1	NM_001136039.2		c.9A>G	p.Ser3Ser	synonymous	Exon 2 of 7	NP_001129511.1	Q9GZT8-1
	NIF3L1	NM_001369442.1		c.9A>G	p.Ser3Ser	synonymous	Exon 2 of 7	NP_001356371.1	Q9GZT8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIF3L1	ENST00000409020.6	TSL:5 MANE Select	c.9A>G	p.Ser3Ser	synonymous	Exon 2 of 7	ENSP00000386394.1	Q9GZT8-1
	NIF3L1	ENST00000409588.1	TSL:1	c.9A>G	p.Ser3Ser	synonymous	Exon 1 of 5	ENSP00000387021.1	Q9GZT8-3
	NIF3L1	ENST00000359683.8	TSL:1	c.-56-17A>G		intron	N/A	ENSP00000352711.4	Q9GZT8-2

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

GnomAD2 exomes AF: 0.000862 AC: 205 AN: 237744 AF XY: 0.000612

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 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

African (AFR) AF: 0.0117 AC: 389 AN: 33256

American (AMR) AF: 0.000534 AC: 23 AN: 43092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25664

East Asian (EAS) AF: 0.00 AC: 0 AN: 39554

South Asian (SAS) AF: 0.00 AC: 0 AN: 85394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53142

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5756

European-Non Finnish (NFE) AF: 0.0000732 AC: 81 AN: 1106100

Other (OTH) AF: 0.000833 AC: 50 AN: 60020

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

African (AFR) AF: 0.0120 AC: 499 AN: 41548

American (AMR) AF: 0.00163 AC: 25 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68010

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00164 Hom.: 0

Bravo AF: 0.00388

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.5
DANN	Benign	0.63
PhyloP100		-0.0070
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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

Other links and lift over

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