rs374238178

Variant names:

• chr19-35269466-C-A
• rs374238178
• NM_003367.4:c.83C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-35269466-C-A
• chr19-35269466-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003367.4(USF2):​c.83C>A​(p.Ala28Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,547,432 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: USF2 NM_003367.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

Genes affected

USF2 (HGNC:12594): (upstream transcription factor 2, c-fos interacting) This gene encodes a member of the basic helix-loop-helix leucine zipper family of transcription factors. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs and is involved in regulating multiple cellular processes. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10427427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF2	NM_003367.4	c.83C>A	p.Ala28Glu	missense_variant	Exon 2 of 10	ENST00000222305.8	NP_003358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF2	ENST00000222305.8	c.83C>A	p.Ala28Glu	missense_variant	Exon 2 of 10	1	NM_003367.4	ENSP00000222305.2

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 150168 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000489

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397264 Hom.: 0 Cov.: 33 AF XY: 0.00000144 AC XY: 1 AN XY: 693868

Gnomad4 AFR exome AF: 0.0000683

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 150168 Hom.: 0 Cov.: 28 AF XY: 0.0000136 AC XY: 1 AN XY: 73288

Gnomad4 AFR AF: 0.0000489

Gnomad4 AMR AF: 0.0000661

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.077	.;T;.;.;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.82	T;T;T;T;T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.69	N;N;N;N;.
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.46	N;N;.;N;.
REVEL	Uncertain	0.29
Sift	Benign	1.0	T;T;.;D;.
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.10	B;B;.;.;B
Vest4		0.38
MutPred		0.14		.;.;.;.;Loss of sheet (P = 0.0104);
MVP		0.21
MPC		0.95
ClinPred		0.12	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.13
gMVP		0.090

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: rs374238178; hg19: chr19-35760369;