rs2394882

Variant names:

• chr6-31164872-A-C
• rs2394882
• NM_002701.6:c.817-5T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-31164872-A-C
• chr6-31164872-A-G
• chr6-31164872-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002701.6(POU5F1):​c.817-5T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,609,460 control chromosomes in the GnomAD database, including 360,389 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (36757 hom., cov: 33)
  • Exomes 𝑓: 0.66 (323632 hom.)
• Consequence: POU5F1 NM_002701.6 splice_region, intron
• Scores: Splicing: ADA: 0.05026
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 36 publications found

Genes affected

POU5F1 (HGNC:9221): (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

TCF19 (HGNC:11629): (transcription factor 19) This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.817-5T>G		splice_region_variant, intron_variant	Intron 4 of 4	ENST00000259915.13	NP_002692.2
POU5F1	NM_001173531.3	c.307-5T>G		splice_region_variant, intron_variant	Intron 4 of 4		NP_001167002.1
POU5F1	NM_203289.6	c.307-5T>G		splice_region_variant, intron_variant	Intron 3 of 3		NP_976034.4
POU5F1	NM_001285986.2	c.229-5T>G		splice_region_variant, intron_variant	Intron 2 of 2		NP_001272915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.817-5T>G		splice_region_variant, intron_variant	Intron 4 of 4	1	NM_002701.6	ENSP00000259915.7

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104940 AN: 151924 Hom.: 36727 Cov.: 33

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.695

GnomAD2 exomes AF: 0.642 AC: 154716 AN: 240940 AF XY: 0.640

Gnomad AFR exome AF: 0.789

Gnomad AMR exome AF: 0.596

Gnomad ASJ exome AF: 0.718

Gnomad EAS exome AF: 0.651

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.659

Gnomad OTH exome AF: 0.671

GnomAD4 exome AF: 0.665 AC: 968539 AN: 1457418 Hom.: 323632 Cov.: 85 AF XY: 0.661 AC XY: 479421 AN XY: 724794

African (AFR) AF: 0.796 AC: 26608 AN: 33414

American (AMR) AF: 0.608 AC: 26863 AN: 44184

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 18737 AN: 26082

East Asian (EAS) AF: 0.600 AC: 23764 AN: 39582

South Asian (SAS) AF: 0.583 AC: 49999 AN: 85826

European-Finnish (FIN) AF: 0.577 AC: 30084 AN: 52162

Middle Eastern (MID) AF: 0.690 AC: 3975 AN: 5758

European-Non Finnish (NFE) AF: 0.674 AC: 747860 AN: 1110154

Other (OTH) AF: 0.675 AC: 40649 AN: 60256

GnomAD4 genome AF: 0.691 AC: 105019 AN: 152042 Hom.: 36757 Cov.: 33 AF XY: 0.685 AC XY: 50868 AN XY: 74304

African (AFR) AF: 0.792 AC: 32846 AN: 41496

American (AMR) AF: 0.679 AC: 10362 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2521 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3277 AN: 5160

South Asian (SAS) AF: 0.568 AC: 2741 AN: 4826

European-Finnish (FIN) AF: 0.568 AC: 5983 AN: 10530

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.663 AC: 45046 AN: 67980

Other (OTH) AF: 0.694 AC: 1464 AN: 2110

Alfa AF: 0.676 Hom.: 141191

Bravo AF: 0.705

Asia WGS AF: 0.665 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.62
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.050
dbscSNV1_RF	Benign	0.28
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: rs2394882; hg19: chr6-31132649; COSMIC: COSV52565439; COSMIC: COSV52565439;