chr3-156979223-T-C

Variant names:

• chr3-156979223-T-C
• rs372814129
• NM_001004316.3:c.775T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001004316.3(LEKR1):​c.775T>C​(p.Leu259Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000176 in 1,135,248 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: LEKR1 NM_001004316.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 0 publications found

Genes affected

LEKR1 (HGNC:33765): (leucine, glutamate and lysine rich 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=0.114 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004316.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEKR1	NM_001004316.3	MANE Select	c.775T>C	p.Leu259Leu	synonymous	Exon 7 of 13	NP_001004316.2	J3KP02

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEKR1	ENST00000356539.9	TSL:5 MANE Select	c.775T>C	p.Leu259Leu	synonymous	Exon 7 of 13	ENSP00000348936.4	J3KP02
	LEKR1	ENST00000470811.6	TSL:2	n.775T>C		non_coding_transcript_exon	Exon 7 of 14	ENSP00000418214.2	A0A8I5FW65
	LEKR1	ENST00000489350.5	TSL:3	n.476T>C		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000176 AC: 2 AN: 1135248 Hom.: 0 Cov.: 26 AF XY: 0.00000359 AC XY: 2 AN XY: 557216

African (AFR) AF: 0.00 AC: 0 AN: 24362

American (AMR) AF: 0.00 AC: 0 AN: 28258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15930

East Asian (EAS) AF: 0.00 AC: 0 AN: 12830

South Asian (SAS) AF: 0.00 AC: 0 AN: 76126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4392

European-Non Finnish (NFE) AF: 0.00000218 AC: 2 AN: 917780

Other (OTH) AF: 0.00 AC: 0 AN: 41408

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.71
PhyloP100		0.11

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: rs372814129; hg19: chr3-156697012;