rs72974768

Positions:

• chr19-3435547-G-A
• chr19-3435547-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001245002.2(NFIC):​c.958+340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 152,278 control chromosomes in the GnomAD database, including 212 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 0.040 (212 hom., cov: 32)
• Consequence: NFIC NM_001245002.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NFIC	NM_001245002.2	c.958+340G>A		intron_variant		ENST00000443272.3	NP_001231931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFIC	ENST00000443272.3	c.958+340G>A		intron_variant		2	NM_001245002.2	ENSP00000396843	P1

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6128 AN: 152160 Hom.: 212 Cov.: 32

Gnomad AFR AF: 0.00885

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0940

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0439

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

GnomAD4 genome AF: 0.0402 AC: 6128 AN: 152278 Hom.: 212 Cov.: 32 AF XY: 0.0421 AC XY: 3138 AN XY: 74456

Gnomad4 AFR AF: 0.00883

Gnomad4 AMR AF: 0.0264

Gnomad4 ASJ AF: 0.0940

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0484

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0471 Hom.: 55

Bravo AF: 0.0322

Asia WGS AF: 0.0180 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.89

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: rs72974768; hg19: chr19-3435545;