chr13-32314943-A-G

Position:

• chr13-32314943-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001136571.2(ZAR1L):​c.-390+372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 152,260 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

• Frequency: Genomes: 𝑓 0.038 (352 hom., cov: 32)
• Consequence: ZAR1L NM_001136571.2 intron
• Clinical Significance: Benign reviewed by expert panel B:1
• Conservation: PhyloP100: -0.0210

Genes affected

ZAR1L (HGNC:37116): (zygote arrest 1 like) This gene encodes a member of the ZAR1 family that is predominantly expressed in oocytes and early embryos. The protein may function as an RNA regulator in early embryos. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-32314943-A-G is Benign according to our data. Variant chr13-32314943-A-G is described in ClinVar as [Benign]. Clinvar id is 209597.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr13-32314943-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAR1L	NM_001136571.2	c.-390+372T>C		intron_variant		ENST00000533490.7	NP_001130043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAR1L	ENST00000533490.7	c.-390+372T>C		intron_variant		5	NM_001136571.2	ENSP00000437289	P1

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 5753 AN: 152144 Hom.: 353 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0258

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

GnomAD4 genome AF: 0.0378 AC: 5753 AN: 152260 Hom.: 352 Cov.: 32 AF XY: 0.0365 AC XY: 2716 AN XY: 74452

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0377 Hom.: 62

Bravo AF: 0.0424

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: reviewed by expert panel

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 2 Benign:1

Benign, reviewed by expert panel

curation

Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)

Jan 12, 2015

Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.14 (African), derived from 1000 genomes (2012-04-30). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7988901; hg19: chr13-32889080;