19-3414022-T-C

Position:

• chr19-3414022-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

NFIC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIC	NM_001245002.2	c.563-11084T>C		intron_variant		ENST00000443272.3	NP_001231931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIC	ENST00000443272.3	c.563-11084T>C		intron_variant		2	NM_001245002.2	ENSP00000396843.2

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

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.956

Gnomad4 ASJ AF: 0.955

Gnomad4 EAS AF: 0.969

Gnomad4 SAS AF: 0.926

Gnomad4 FIN AF: 0.973

Gnomad4 NFE AF: 0.929

Gnomad4 OTH AF: 0.947

Alfa AF: 0.931 Hom.: 86605

Bravo AF: 0.944

Asia WGS AF: 0.940 AC: 3271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.28

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: rs4806933; hg19: chr19-3414020;