19-3428836-G-C

Variant names:

• chr19-3428836-G-C
• rs7507204
• NM_001245002.2:c.634+3659G>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.634+3659G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 151,796 control chromosomes in the GnomAD database, including 4,162 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 0.21 (4162 hom., cov: 29)
• Consequence: NFIC NM_001245002.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 28 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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIC	NM_001245002.2	MANE Select	c.634+3659G>C		intron	N/A	NP_001231931.1
	NFIC	NM_205843.3		c.607+3659G>C		intron	N/A	NP_995315.1
	NFIC	NM_001245004.2		c.634+3659G>C		intron	N/A	NP_001231933.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFIC	ENST00000443272.3	TSL:2 MANE Select	c.634+3659G>C		intron	N/A	ENSP00000396843.2
	NFIC	ENST00000589123.6	TSL:1	c.607+3659G>C		intron	N/A	ENSP00000465655.1
	NFIC	ENST00000341919.8	TSL:1	c.634+3659G>C		intron	N/A	ENSP00000342194.2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31512 AN: 151680 Hom.: 4158 Cov.: 29

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.208 AC: 31518 AN: 151796 Hom.: 4162 Cov.: 29 AF XY: 0.212 AC XY: 15754 AN XY: 74160

African (AFR) AF: 0.0974 AC: 4040 AN: 41492

American (AMR) AF: 0.286 AC: 4360 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3102 AN: 5102

South Asian (SAS) AF: 0.253 AC: 1212 AN: 4798

European-Finnish (FIN) AF: 0.248 AC: 2609 AN: 10516

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15285 AN: 67864

Other (OTH) AF: 0.177 AC: 373 AN: 2110

Alfa AF: 0.111 Hom.: 179

Bravo AF: 0.212

Asia WGS AF: 0.350 AC: 1214 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.3
DANN	Benign	0.89
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs7507204; hg19: chr19-3428834;