chr7-134234280-T-C

Variant names:

• chr7-134234280-T-C
• rs1421477
• NM_144648.3:c.1983+12362T>C

Variant summary

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

The NM_144648.3(LRGUK):​c.1983+12362T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 151,860 control chromosomes in the GnomAD database, including 60,974 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 0.90 (60974 hom., cov: 29)
• Consequence: LRGUK NM_144648.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 1 publications found

Genes affected

LRGUK (HGNC:21964): (leucine rich repeats and guanylate kinase domain containing) Predicted to enable guanylate kinase activity. Predicted to be involved in axoneme assembly and spermatogenesis. Predicted to be located in acrosomal vesicle and manchette. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRGUK	NM_144648.3	c.1983+12362T>C		intron_variant	Intron 16 of 19	ENST00000285928.3	NP_653249.1
LRGUK	XM_024446659.2	c.1983+12362T>C		intron_variant	Intron 16 of 19		XP_024302427.1
LRGUK	XM_024446661.2	c.1983+12362T>C		intron_variant	Intron 16 of 19		XP_024302429.1
LRGUK	XM_047419890.1	c.1776+12362T>C		intron_variant	Intron 14 of 17		XP_047275846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRGUK	ENST00000285928.3	c.1983+12362T>C		intron_variant	Intron 16 of 19	1	NM_144648.3	ENSP00000285928.2

Frequencies

GnomAD3 genomes AF: 0.895 AC: 135874 AN: 151742 Hom.: 60916 Cov.: 29

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.896 AC: 135992 AN: 151860 Hom.: 60974 Cov.: 29 AF XY: 0.898 AC XY: 66614 AN XY: 74198

African (AFR) AF: 0.851 AC: 35177 AN: 41342

American (AMR) AF: 0.929 AC: 14168 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3021 AN: 3472

East Asian (EAS) AF: 0.829 AC: 4271 AN: 5150

South Asian (SAS) AF: 0.901 AC: 4314 AN: 4788

European-Finnish (FIN) AF: 0.948 AC: 10024 AN: 10572

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.912 AC: 61965 AN: 67976

Other (OTH) AF: 0.892 AC: 1882 AN: 2110

Alfa AF: 0.907 Hom.: 124463

Bravo AF: 0.892

Asia WGS AF: 0.859 AC: 2988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.60
PhyloP100		-2.3
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: rs1421477; hg19: chr7-133919032;