NM_001245002.2:c.563-11084T>C

Variant names:

• chr19-3414022-T-C
• rs4806933
• NM_001245002.2:c.563-11084T>C

Variant summary

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

The NM_001245002.2(NFIC):​c.563-11084T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,158 control chromosomes in the GnomAD database, including 67,830 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 0.94 (67830 hom., cov: 31)
• Consequence: NFIC NM_001245002.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

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.563-11084T>C		intron	N/A	NP_001231931.1	P08651-1
	NFIC	NM_205843.3		c.536-11084T>C		intron	N/A	NP_995315.1	P08651-2
	NFIC	NM_001245004.2		c.563-11084T>C		intron	N/A	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.563-11084T>C		intron	N/A	ENSP00000396843.2	P08651-1
	NFIC	ENST00000589123.6	TSL:1	c.536-11084T>C		intron	N/A	ENSP00000465655.1	P08651-2
	NFIC	ENST00000341919.8	TSL:1	c.563-11084T>C		intron	N/A	ENSP00000342194.2	P08651-5

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143511 AN: 152038 Hom.: 67774 Cov.: 31

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.956

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.947

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

GnomAD4 genome AF: 0.944 AC: 143625 AN: 152158 Hom.: 67830 Cov.: 31 AF XY: 0.947 AC XY: 70411 AN XY: 74386

African (AFR) AF: 0.955 AC: 39658 AN: 41508

American (AMR) AF: 0.956 AC: 14579 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 3317 AN: 3472

East Asian (EAS) AF: 0.969 AC: 4995 AN: 5156

South Asian (SAS) AF: 0.926 AC: 4460 AN: 4816

European-Finnish (FIN) AF: 0.973 AC: 10323 AN: 10608

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.929 AC: 63203 AN: 68036

Other (OTH) AF: 0.947 AC: 2000 AN: 2112

Alfa AF: 0.932 Hom.: 102151

Bravo AF: 0.944

Asia WGS AF: 0.940 AC: 3271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.28
PhyloP100		-0.69
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: rs4806933; hg19: chr19-3414020;