rs2035545

Variant names:

• chr12-57083648-T-A
• rs2035545
• ENST00000553654.1:n.113+4303A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57083648-T-A
• chr12-57083648-T-C

Variant summary

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

The ENST00000553654.1(NEMP1):​n.113+4303A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,322 control chromosomes in the GnomAD database, including 767 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 0.098 (767 hom., cov: 33)
• Consequence: NEMP1 ENST00000553654.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 4 publications found

Genes affected

NEMP1 (HGNC:29001): (nuclear envelope integral membrane protein 1) Involved in nuclear membrane organization. Predicted to be located in nuclear inner membrane. Predicted to be integral component of membrane. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000304975 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEMP1	XM_011538056.3	c.271+4166A>T		intron_variant	Intron 1 of 8		XP_011536358.1
NEMP1	XM_024448900.1	c.151+2901A>T		intron_variant	Intron 2 of 9		XP_024304668.1
NEMP1	XM_047428587.1	c.151+2901A>T		intron_variant	Intron 1 of 8		XP_047284543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEMP1	ENST00000553654.1	n.113+4303A>T		intron_variant	Intron 1 of 2	5
ENSG00000304975	ENST00000807484.1	n.*82A>T		downstream_gene_variant
ENSG00000304975	ENST00000807485.1	n.*85A>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14875 AN: 152204 Hom.: 768 Cov.: 33

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0977 AC: 14881 AN: 152322 Hom.: 767 Cov.: 33 AF XY: 0.101 AC XY: 7500 AN XY: 74484

African (AFR) AF: 0.0736 AC: 3060 AN: 41568

American (AMR) AF: 0.127 AC: 1941 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 313 AN: 3472

East Asian (EAS) AF: 0.190 AC: 988 AN: 5188

South Asian (SAS) AF: 0.111 AC: 538 AN: 4830

European-Finnish (FIN) AF: 0.122 AC: 1291 AN: 10604

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0947 AC: 6444 AN: 68032

Other (OTH) AF: 0.0932 AC: 197 AN: 2114

Alfa AF: 0.0392 Hom.: 29

Bravo AF: 0.0952

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.50
PhyloP100		-0.068

Splicing

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

Other links and lift over

dbSNP: rs2035545; hg19: chr12-57477431;