1-167415742-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002697.4(POU2F1):c.2233T>C(p.Ser745Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000813 in 1,614,076 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00080 (3 hom.)
• Consequence: POU2F1 NM_002697.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.44

Genes affected

POU2F1 (HGNC:9212): (POU class 2 homeobox 1) The OCT1 transcription factor was among the first identified members of the POU transcription factor family (summarized by Sturm et al., 1993 [PubMed 8314572]). Members of this family contain the POU domain, a 160-amino acid region necessary for DNA binding to the octameric sequence ATGCAAAT.[supplied by OMIM, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0076306164).
• BP6: Variant 1-167415742-T-C is Benign according to our data. Variant chr1-167415742-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 708859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU2F1	NM_002697.4	c.2233T>C	p.Ser745Pro	missense_variant	16/16	ENST00000367866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU2F1	ENST00000367866.7	c.2233T>C	p.Ser745Pro	missense_variant	16/16	1	NM_002697.4	A1

Frequencies

GnomAD3 genomes AF: 0.000947 AC: 144 AN: 152070 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00635

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00133 AC: 335 AN: 251260 Hom.: 1 AF XY: 0.00140 AC XY: 190 AN XY: 135790

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00745

Gnomad EAS exome AF: 0.00370

Gnomad SAS exome AF: 0.00245

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000608

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000800 AC: 1169 AN: 1461888 Hom.: 3 Cov.: 32 AF XY: 0.000901 AC XY: 655 AN XY: 727248

Gnomad4 AFR exome AF: 0.000717

Gnomad4 AMR exome AF: 0.000827

Gnomad4 ASJ exome AF: 0.00654

Gnomad4 EAS exome AF: 0.00368

Gnomad4 SAS exome AF: 0.00279

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000369

Gnomad4 OTH exome AF: 0.00149

GnomAD4 genome AF: 0.000946 AC: 144 AN: 152188 Hom.: 0 Cov.: 31 AF XY: 0.000901 AC XY: 67 AN XY: 74392

Gnomad4 AFR AF: 0.000963

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00635

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00120 Hom.: 1

Bravo AF: 0.00105

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.00121 AC: 147

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 27, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Uncertain	0.090
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.0053
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.0076	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationTaster	Benign	0.73	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.84	N;N;N;N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Benign	0.27	T;T;T;T
Polyphen		0.31, 0.43	.;.;B;B
Vest4		0.42
MVP		0.92
MPC		1.2
ClinPred		0.035	T
GERP RS		4.2
Varity_R		0.16
gMVP		0.42

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: rs34379394; hg19: chr1-167384979;