2-51759851-T-C

Variant names:

• chr2-51759851-T-C
• rs2176221
• ENST00000440698.1:n.754-2238T>C

Variant summary

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

The ENST00000440698.1(NRXN1-DT):​n.754-2238T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 150,344 control chromosomes in the GnomAD database, including 17,364 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 0.45 (17364 hom., cov: 32)
• Consequence: NRXN1-DT ENST00000440698.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 1 publications found

Genes affected

NRXN1-DT (HGNC:52686): (NRXN1 divergent transcript)

ENSG00000309808 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRXN1-DT	NR_135237.1	n.754-2238T>C		intron_variant	Intron 5 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRXN1-DT	ENST00000440698.1	n.754-2238T>C		intron_variant	Intron 5 of 10	2
NRXN1-DT	ENST00000843923.1	n.46-2238T>C		intron_variant	Intron 1 of 2
ENSG00000309808	ENST00000844064.1	n.441-15699A>G		intron_variant	Intron 1 of 1
ENSG00000309808	ENST00000844065.1	n.411-10472A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 67476 AN: 150228 Hom.: 17287 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.450 AC: 67620 AN: 150344 Hom.: 17364 Cov.: 32 AF XY: 0.455 AC XY: 33433 AN XY: 73502

African (AFR) AF: 0.677 AC: 27945 AN: 41304

American (AMR) AF: 0.502 AC: 7560 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1087 AN: 3432

East Asian (EAS) AF: 0.564 AC: 2885 AN: 5114

South Asian (SAS) AF: 0.603 AC: 2908 AN: 4820

European-Finnish (FIN) AF: 0.342 AC: 3603 AN: 10532

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20256 AN: 66794

Other (OTH) AF: 0.431 AC: 899 AN: 2088

Alfa AF: 0.260 Hom.: 702

Bravo AF: 0.471

Asia WGS AF: 0.614 AC: 2130 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.56
DANN	Benign	0.66
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs2176221; hg19: chr2-51986989;