1-167370211-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_002697.4(POU2F1):c.279A>G(p.Val93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 1,601,502 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (22 hom.)
• Consequence: POU2F1 NM_002697.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.85

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 1-167370211-A-G is Benign according to our data. Variant chr1-167370211-A-G is described in ClinVar as [Benign]. Clinvar id is 777940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.85 with no splicing effect.
• BS2: High AC in GnomAd at 619 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU2F1	NM_002697.4	c.279A>G	p.Val93=	synonymous_variant	4/16	ENST00000367866.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU2F1	ENST00000367866.7	c.279A>G	p.Val93=	synonymous_variant	4/16	1	NM_002697.4	A1

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 619 AN: 152148 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00387

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00679

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00380 AC: 952 AN: 250390 Hom.: 1 AF XY: 0.00378 AC XY: 511 AN XY: 135318

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.00408

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.00384

Gnomad NFE exome AF: 0.00596

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.00552 AC: 7995 AN: 1449236 Hom.: 22 Cov.: 29 AF XY: 0.00541 AC XY: 3900 AN XY: 720644

Gnomad4 AFR exome AF: 0.00132

Gnomad4 AMR exome AF: 0.00236

Gnomad4 ASJ exome AF: 0.00360

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000832

Gnomad4 FIN exome AF: 0.00489

Gnomad4 NFE exome AF: 0.00648

Gnomad4 OTH exome AF: 0.00459

GnomAD4 genome AF: 0.00407 AC: 619 AN: 152266 Hom.: 2 Cov.: 32 AF XY: 0.00367 AC XY: 273 AN XY: 74458

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00387

Gnomad4 NFE AF: 0.00679

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00577 Hom.: 1

Bravo AF: 0.00375

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	7.2
Dann	Benign	0.83

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: rs41270710; hg19: chr1-167339448;