rs72974768

Variant names:

• chr19-3435547-G-A
• rs72974768
• NM_001245002.2:c.958+340G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3435547-G-A
• chr19-3435547-G-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.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
• Publications: 5 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=-0.88).
• 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 rank	MANE	Protein	UniProt
NFIC	NM_001245002.2	c.958+340G>A		intron_variant	Intron 6 of 10	ENST00000443272.3	NP_001231931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFIC	ENST00000443272.3	c.958+340G>A		intron_variant	Intron 6 of 10	2	NM_001245002.2	ENSP00000396843.2

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

African (AFR) AF: 0.00883 AC: 367 AN: 41568

American (AMR) AF: 0.0264 AC: 403 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0940 AC: 326 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0484 AC: 234 AN: 4830

European-Finnish (FIN) AF: 0.103 AC: 1089 AN: 10602

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0520 AC: 3538 AN: 68010

Other (OTH) AF: 0.0435 AC: 92 AN: 2116

Alfa AF: 0.0413 Hom.: 155

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
PhyloP100		0.058
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: rs72974768; hg19: chr19-3435545;