NM_001245002.2:c.550G>C

Variant names:

• chr19-3382231-G-C
• rs201510675
• NM_001245002.2:c.550G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001245002.2(NFIC):​c.550G>C​(p.Val184Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000178 in 1,601,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: NFIC NM_001245002.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18
• Publications: 1 publications found

Genes affected

NFIC (HGNC:7786): (nuclear factor I C) The protein encoded by this gene belongs to the CTF/NF-I family. These are dimeric DNA-binding proteins, and function as cellular transcription factors and as replication factors for adenovirus DNA replication. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018574387).
• BS2: High AC in GnomAd4 at 48 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001245002.2. 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
	NFIC	NM_001245002.2	MANE Select	c.550G>C	p.Val184Leu	missense	Exon 2 of 11	NP_001231931.1	P08651-1
	NFIC	NM_205843.3		c.523G>C	p.Val175Leu	missense	Exon 2 of 11	NP_995315.1	P08651-2
	NFIC	NM_001245004.2		c.550G>C	p.Val184Leu	missense	Exon 2 of 10	NP_001231933.1	P08651-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIC	ENST00000443272.3	TSL:2 MANE Select	c.550G>C	p.Val184Leu	missense	Exon 2 of 11	ENSP00000396843.2	P08651-1
	NFIC	ENST00000589123.6	TSL:1	c.523G>C	p.Val175Leu	missense	Exon 2 of 11	ENSP00000465655.1	P08651-2
	NFIC	ENST00000341919.8	TSL:1	c.550G>C	p.Val184Leu	missense	Exon 2 of 9	ENSP00000342194.2	P08651-5

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000260 AC: 62 AN: 238668 AF XY: 0.000238

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00464

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000119

Gnomad OTH exome AF: 0.000499

GnomAD4 exome AF: 0.000164 AC: 237 AN: 1449474 Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 107 AN XY: 721266

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00495 AC: 129 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.0000232 AC: 1 AN: 43114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5404

European-Non Finnish (NFE) AF: 0.0000765 AC: 85 AN: 1110774

Other (OTH) AF: 0.000365 AC: 22 AN: 60224

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68048

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000814 Hom.: 0

Bravo AF: 0.000174

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000353 AC: 3

ExAC AF: 0.000207 AC: 25

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.15
Sift	Benign	0.091	T
Sift4G	Benign	0.18	T
Polyphen		0.068	B
Vest4		0.53
MutPred		0.50		Gain of helix (P = 0.0425)
MVP		0.62
MPC		0.50
ClinPred		0.094	T
GERP RS		1.4
Varity_R		0.028
gMVP		0.92
Mutation Taster		=68/32	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: rs201510675; hg19: chr19-3382229;