2-1546537-T-C

Variant names:

• chr2-1546537-T-C
• rs6705087
• NR_198951.1:n.2951A>G

Variant summary

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

The NR_198948.1(LALTOP):​n.3395+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,076 control chromosomes in the GnomAD database, including 35,904 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 0.68 (35900 hom., cov: 32)
  • Exomes 𝑓: 0.64 (4 hom.)
• Consequence: LALTOP NR_198948.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 4 publications found

Genes affected

LALTOP (HGNC:58132):

ENSG00000231482 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_198948.1. 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
	LALTOP	NR_198951.1		n.2951A>G		non_coding_transcript_exon	Exon 4 of 4
	LALTOP	NR_198948.1		n.3395+7A>G		splice_region intron	N/A
	LALTOP	NR_198949.1		n.3395+7A>G		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000231482	ENST00000650512.1		n.547+33664A>G		intron	N/A
	LALTOP	ENST00000816433.1		n.520+7A>G		splice_region intron	N/A
	LALTOP	ENST00000816434.1		n.654+7A>G		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104004 AN: 151936 Hom.: 35841 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.670

GnomAD4 exome AF: 0.636 AC: 14 AN: 22 Hom.: 4 AF XY: 0.500 AC XY: 7 AN XY: 14

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.625 AC: 5 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 7 AN: 10

Other (OTH) AF: 0.500 AC: 2 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000610614), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.685 AC: 104127 AN: 152054 Hom.: 35900 Cov.: 32 AF XY: 0.684 AC XY: 50818 AN XY: 74330

African (AFR) AF: 0.781 AC: 32390 AN: 41462

American (AMR) AF: 0.628 AC: 9600 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2366 AN: 3470

East Asian (EAS) AF: 0.655 AC: 3370 AN: 5142

South Asian (SAS) AF: 0.619 AC: 2987 AN: 4822

European-Finnish (FIN) AF: 0.657 AC: 6955 AN: 10578

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.651 AC: 44283 AN: 67986

Other (OTH) AF: 0.676 AC: 1427 AN: 2110

Alfa AF: 0.664 Hom.: 11938

Bravo AF: 0.688

Asia WGS AF: 0.664 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.16
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs6705087; hg19: chr2-1550309;