19-3432254-A-G

Variant names:

• chr19-3432254-A-G
• rs4806934
• NM_001245002.2:c.635-1264A>G

Variant summary

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

The NM_001245002.2(NFIC):​c.635-1264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,992 control chromosomes in the GnomAD database, including 19,883 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 0.49 (19883 hom., cov: 32)
• Consequence: NFIC NM_001245002.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NFIC	NM_001245002.2	c.635-1264A>G		intron_variant	Intron 3 of 10	ENST00000443272.3	NP_001231931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIC	ENST00000443272.3	c.635-1264A>G		intron_variant	Intron 3 of 10	2	NM_001245002.2	ENSP00000396843.2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73615 AN: 151874 Hom.: 19836 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.485 AC: 73720 AN: 151992 Hom.: 19883 Cov.: 32 AF XY: 0.489 AC XY: 36334 AN XY: 74286

African (AFR) AF: 0.691 AC: 28635 AN: 41442

American (AMR) AF: 0.559 AC: 8539 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3912 AN: 5172

South Asian (SAS) AF: 0.491 AC: 2365 AN: 4812

European-Finnish (FIN) AF: 0.336 AC: 3550 AN: 10558

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24424 AN: 67952

Other (OTH) AF: 0.442 AC: 933 AN: 2110

Alfa AF: 0.396 Hom.: 39748

Bravo AF: 0.510

Asia WGS AF: 0.589 AC: 2046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs4806934; hg19: chr19-3432252;