chr2-73673773-T-G

Variant names:

• chr2-73673773-T-G
• rs10206899
• ENST00000450720.5:n.738-40T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000755955.1(ALMS1P1):​n.8T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 28)
  • Exomes 𝑓: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALMS1P1 ENST00000755955.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783
• Publications: 43 publications found

Genes affected

ALMS1P1 (HGNC:):

ALMS1P1 (HGNC:29586): (ALMS1 pseudogene 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALMS1P1	NR_003683.2	n.738-40T>G		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALMS1P1	ENST00000450720.5	n.738-40T>G		intron_variant	Intron 4 of 6	1
ALMS1P1	ENST00000755955.1	n.8T>G		non_coding_transcript_exon_variant	Exon 1 of 2
ALMS1P1	ENST00000428767.1	n.550-40T>G		intron_variant	Intron 3 of 5	6

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.0000387 AC: 6 AN: 154944 AF XY: 0.0000242

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000889

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.0000331

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000153 AC: 1 AN: 655564 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 346002

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

African (AFR) AF: 0.00 AC: 0 AN: 16218

American (AMR) AF: 0.00 AC: 0 AN: 31344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17856

East Asian (EAS) AF: 0.00 AC: 0 AN: 26950

South Asian (SAS) AF: 0.00 AC: 0 AN: 64352

European-Finnish (FIN) AF: 0.0000257 AC: 1 AN: 38872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2800

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 426976

Other (OTH) AF: 0.00 AC: 0 AN: 30196

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.88
DANN	Benign	0.34
PhyloP100		-0.78

Splicing

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

Other links and lift over

dbSNP: rs10206899; hg19: chr2-73900900;