4-2184187-T-C

Variant names:

• chr4-2184187-T-C
• rs7659386
• NM_181808.4:c.1022-4722A>G

Variant summary

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

The NM_181808.4(POLN):​c.1022-4722A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 139,952 control chromosomes in the GnomAD database, including 6,321 homozygotes. 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 0.24 (6321 hom., cov: 25)
• Consequence: POLN NM_181808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 3 publications found

Genes affected

POLN (HGNC:18870): (DNA polymerase nu) This gene encodes a DNA polymerase type-A family member. The encoded protein plays a role in DNA repair and homologous recombination. This gene shares its 5' exons with some transcripts from overlapping GeneID: 79441, which encodes an augmentin-like protein complex subunit. [provided by RefSeq, Dec 2014]

ENSG00000290263 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLN	NM_181808.4	c.1022-4722A>G		intron_variant	Intron 7 of 25	ENST00000511885.6	NP_861524.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLN	ENST00000511885.6	c.1022-4722A>G		intron_variant	Intron 7 of 25	5	NM_181808.4	ENSP00000435506.1
ENSG00000290263	ENST00000672725.1	n.2611+9017A>G		intron_variant	Intron 9 of 18			ENSP00000500518.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 33754 AN: 139936 Hom.: 6316 Cov.: 25

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.248

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.241 AC: 33774 AN: 139952 Hom.: 6321 Cov.: 25 AF XY: 0.239 AC XY: 16230 AN XY: 67920

African (AFR) AF: 0.508 AC: 18864 AN: 37100

American (AMR) AF: 0.241 AC: 3380 AN: 14052

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 538 AN: 3318

East Asian (EAS) AF: 0.374 AC: 1824 AN: 4880

South Asian (SAS) AF: 0.169 AC: 723 AN: 4278

European-Finnish (FIN) AF: 0.0625 AC: 536 AN: 8576

Middle Eastern (MID) AF: 0.229 AC: 65 AN: 284

European-Non Finnish (NFE) AF: 0.111 AC: 7159 AN: 64614

Other (OTH) AF: 0.248 AC: 483 AN: 1950

Alfa AF: 0.119 Hom.: 850

Bravo AF: 0.273

Asia WGS AF: 0.315 AC: 1088 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.7
DANN	Benign	0.46
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7659386; hg19: chr4-2185914; COSMIC: COSV67027095; COSMIC: COSV67027095;