ENST00000450720.5:n.738-40T>C

Variant names:

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

Variant summary

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

The ENST00000450720.5(ALMS1P1):​n.738-40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 802,780 control chromosomes in the GnomAD database, including 25,374 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 0.30 (8595 hom., cov: 28)
  • Exomes 𝑓: 0.21 (16779 hom.)
• Consequence: ALMS1P1 ENST00000450720.5 intron
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALMS1P1	NR_003683.2	n.738-40T>C		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>C		intron_variant	Intron 4 of 6	1
ALMS1P1	ENST00000755955.1	n.8T>C		non_coding_transcript_exon_variant	Exon 1 of 2
ALMS1P1	ENST00000428767.1	n.550-40T>C		intron_variant	Intron 3 of 5	6

Frequencies

GnomAD3 genomes AF: 0.303 AC: 44901 AN: 148414 Hom.: 8566 Cov.: 28

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.00492

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.207 AC: 32123 AN: 154944 AF XY: 0.201

Gnomad AFR exome AF: 0.566

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.172

Gnomad EAS exome AF: 0.00365

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.203

GnomAD4 exome AF: 0.210 AC: 137720 AN: 654274 Hom.: 16779 Cov.: 9 AF XY: 0.207 AC XY: 71560 AN XY: 345336

African (AFR) AF: 0.545 AC: 8823 AN: 16192

American (AMR) AF: 0.231 AC: 7242 AN: 31302

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 3064 AN: 17836

East Asian (EAS) AF: 0.00404 AC: 109 AN: 26950

South Asian (SAS) AF: 0.156 AC: 10054 AN: 64328

European-Finnish (FIN) AF: 0.183 AC: 7101 AN: 38816

Middle Eastern (MID) AF: 0.201 AC: 559 AN: 2788

European-Non Finnish (NFE) AF: 0.221 AC: 94260 AN: 425918

Other (OTH) AF: 0.216 AC: 6508 AN: 30144

GnomAD4 genome AF: 0.303 AC: 44979 AN: 148506 Hom.: 8595 Cov.: 28 AF XY: 0.296 AC XY: 21365 AN XY: 72178

African (AFR) AF: 0.542 AC: 21911 AN: 40442

American (AMR) AF: 0.273 AC: 3941 AN: 14458

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 615 AN: 3458

East Asian (EAS) AF: 0.00493 AC: 25 AN: 5066

South Asian (SAS) AF: 0.139 AC: 649 AN: 4664

European-Finnish (FIN) AF: 0.192 AC: 1841 AN: 9598

Middle Eastern (MID) AF: 0.201 AC: 58 AN: 288

European-Non Finnish (NFE) AF: 0.224 AC: 15116 AN: 67588

Other (OTH) AF: 0.288 AC: 588 AN: 2044

Alfa AF: 0.248 Hom.: 4873

Bravo AF: 0.318

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.95
DANN	Benign	0.33
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;