rs1205817

Variant names:

• chr19-42099624-A-G
• rs1205817
• NM_001394376.1:c.476-6T>C

Variant summary

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

The NM_001394376.1(POU2F2):​c.476-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,611,632 control chromosomes in the GnomAD database, including 56,280 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 0.36 (14873 hom., cov: 31)
  • Exomes 𝑓: 0.22 (41407 hom.)
• Consequence: POU2F2 NM_001394376.1 splice_region, intron
• Scores: Splicing: ADA: 0.00008648
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.998
• Publications: 11 publications found

Genes affected

POU2F2 (HGNC:9213): (POU class 2 homeobox 2) The protein encoded by this gene is a homeobox-containing transcription factor of the POU domain family. The encoded protein binds the octamer sequence 5'-ATTTGCAT-3', a common transcription factor binding site in immunoglobulin gene promoters. Several transcript variants encoding different isoforms have been found 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2F2	NM_001394376.1	c.476-6T>C		splice_region_variant, intron_variant	Intron 6 of 14	ENST00000692977.1	NP_001381305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2F2	ENST00000692977.1	c.476-6T>C		splice_region_variant, intron_variant	Intron 6 of 14		NM_001394376.1	ENSP00000509972.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54443 AN: 151856 Hom.: 14822 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.337

GnomAD2 exomes AF: 0.254 AC: 63720 AN: 250422 AF XY: 0.251

Gnomad AFR exome AF: 0.774

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.178

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.215 AC: 314365 AN: 1459658 Hom.: 41407 Cov.: 33 AF XY: 0.218 AC XY: 157988 AN XY: 726252

African (AFR) AF: 0.783 AC: 26181 AN: 33432

American (AMR) AF: 0.243 AC: 10854 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 6631 AN: 26122

East Asian (EAS) AF: 0.168 AC: 6667 AN: 39686

South Asian (SAS) AF: 0.359 AC: 30954 AN: 86192

European-Finnish (FIN) AF: 0.135 AC: 7188 AN: 53398

Middle Eastern (MID) AF: 0.329 AC: 1893 AN: 5756

European-Non Finnish (NFE) AF: 0.188 AC: 209045 AN: 1110092

Other (OTH) AF: 0.248 AC: 14952 AN: 60328

GnomAD4 genome AF: 0.359 AC: 54558 AN: 151974 Hom.: 14873 Cov.: 31 AF XY: 0.355 AC XY: 26352 AN XY: 74310

African (AFR) AF: 0.764 AC: 31663 AN: 41432

American (AMR) AF: 0.270 AC: 4121 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 869 AN: 3470

East Asian (EAS) AF: 0.183 AC: 942 AN: 5154

South Asian (SAS) AF: 0.379 AC: 1825 AN: 4820

European-Finnish (FIN) AF: 0.128 AC: 1356 AN: 10582

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12800 AN: 67936

Other (OTH) AF: 0.339 AC: 714 AN: 2108

Alfa AF: 0.264 Hom.: 6318

Bravo AF: 0.384

Asia WGS AF: 0.373 AC: 1296 AN: 3478

EpiCase AF: 0.194

EpiControl AF: 0.197

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.7
DANN	Benign	0.72
PhyloP100		1.0
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000086
dbscSNV1_RF	Benign	0.034
SpliceAI score (max)		0.040		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: rs1205817; hg19: chr19-42603776; COSMIC: COSV60763522; COSMIC: COSV60763522;