rs1220398

Positions:

• chr1-9934281-A-G
• chr1-9934281-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032368.5(LZIC):​c.336+481T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 151,900 control chromosomes in the GnomAD database, including 44,147 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 0.74 (44147 hom., cov: 30)
• Consequence: LZIC NM_032368.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

Genes affected

LZIC (HGNC:17497): (leucine zipper and CTNNBIP1 domain containing) Predicted to enable beta-catenin binding activity. Predicted to be involved in response to ionizing radiation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LZIC	NM_032368.5	c.336+481T>C		intron_variant		ENST00000377223.6	NP_115744.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LZIC	ENST00000377223.6	c.336+481T>C		intron_variant		1	NM_032368.5	ENSP00000366430.1
LZIC	ENST00000377213.1	c.336+481T>C		intron_variant		1		ENSP00000366418.1
LZIC	ENST00000400903.6	c.336+481T>C		intron_variant		1		ENSP00000383695.2
LZIC	ENST00000488540.5	c.228+481T>C		intron_variant		2		ENSP00000468610.1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112888 AN: 151786 Hom.: 44133 Cov.: 30

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.744 AC: 112939 AN: 151900 Hom.: 44147 Cov.: 30 AF XY: 0.744 AC XY: 55261 AN XY: 74240

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.774

Alfa AF: 0.831 Hom.: 41358

Bravo AF: 0.737

Asia WGS AF: 0.638 AC: 2220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.7
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs1220398; hg19: chr1-9994339;