11-74493934-T-C

Position:

• chr11-74493934-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000528481.5(POLD3):​c.-97T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 407,342 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 34)
  • Exomes 𝑓: 0.0041 (3 hom.)
• Consequence: POLD3 ENST00000528481.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

Genes affected

LIPT2-AS1 (HGNC:):

POLD3 (HGNC:20932): (DNA polymerase delta 3, accessory subunit) This gene encodes the 66-kDa subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. The encoded protein plays a role in regulating the activity of DNA polymerase delta through interactions with other subunits and the processivity cofactor proliferating cell nuclear antigen (PCNA). Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-74493934-T-C is Benign according to our data. Variant chr11-74493934-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00415 (1058/254966) while in subpopulation MID AF= 0.0288 (38/1320). AF 95% confidence interval is 0.0216. There are 3 homozygotes in gnomad4_exome. There are 575 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPT2-AS1	NR_171028.1	n.555T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPT2-AS1	ENST00000526036.1	n.569T>C		non_coding_transcript_exon_variant	1/2	1
POLD3	ENST00000528481.5	c.-97T>C		5_prime_UTR_variant	1/6	2		ENSP00000431239.1

Frequencies

GnomAD3 genomes AF: 0.00314 AC: 478 AN: 152258 Hom.: 3 Cov.: 34

Gnomad AFR AF: 0.000892

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00354

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00415 AC: 1058 AN: 254966 Hom.: 3 Cov.: 0 AF XY: 0.00442 AC XY: 575 AN XY: 130084

Gnomad4 AFR exome AF: 0.000861

Gnomad4 AMR exome AF: 0.00483

Gnomad4 ASJ exome AF: 0.0131

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0186

Gnomad4 FIN exome AF: 0.000276

Gnomad4 NFE exome AF: 0.00409

Gnomad4 OTH exome AF: 0.00446

GnomAD4 genome AF: 0.00314 AC: 479 AN: 152376 Hom.: 2 Cov.: 34 AF XY: 0.00334 AC XY: 249 AN XY: 74526

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00354

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00326 Hom.: 0

Bravo AF: 0.00324

Asia WGS AF: 0.00577 AC: 20 AN: 3478

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

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

ENSG00000254837: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs190250626; hg19: chr11-74204979;