chr1-154024870-G-A

Variant names:

• chr1-154024870-G-A
• rs11264886
• ENST00000368559.8:c.4122+672C>T

Variant summary

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

The ENST00000368559.8(NUP210L):​c.4122+672C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 146,682 control chromosomes in the GnomAD database, including 5,901 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 0.28 (5901 hom., cov: 26)
• Consequence: NUP210L ENST00000368559.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 9 publications found

Genes affected

NUP210L (HGNC:29915): (nucleoporin 210 like) Predicted to act upstream of or within Sertoli cell development and spermatid development. Predicted to be integral component of membrane. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

NUP210L Gene-Disease associations (from GenCC):

• spermatogenic failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP210L	NM_207308.3	c.4122+672C>T		intron_variant	Intron 30 of 39		NP_997191.2
NUP210L	NM_001159484.1	c.4122+672C>T		intron_variant	Intron 30 of 37		NP_001152956.1
NUP210L	XM_017002788.3	c.4122+672C>T		intron_variant	Intron 30 of 38		XP_016858277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP210L	ENST00000368559.8	c.4122+672C>T		intron_variant	Intron 30 of 39	5		ENSP00000357547.3
NUP210L	ENST00000368553.5	c.921+672C>T		intron_variant	Intron 8 of 15	1		ENSP00000357541.1
NUP210L	ENST00000271854.3	c.4122+672C>T		intron_variant	Intron 30 of 37	5		ENSP00000271854.3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 40756 AN: 146612 Hom.: 5888 Cov.: 26

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.327

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.278 AC: 40795 AN: 146682 Hom.: 5901 Cov.: 26 AF XY: 0.284 AC XY: 20165 AN XY: 71064

African (AFR) AF: 0.195 AC: 7744 AN: 39748

American (AMR) AF: 0.380 AC: 5547 AN: 14584

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1008 AN: 3450

East Asian (EAS) AF: 0.286 AC: 1410 AN: 4934

South Asian (SAS) AF: 0.332 AC: 1539 AN: 4630

European-Finnish (FIN) AF: 0.351 AC: 3178 AN: 9054

Middle Eastern (MID) AF: 0.318 AC: 87 AN: 274

European-Non Finnish (NFE) AF: 0.290 AC: 19470 AN: 67078

Other (OTH) AF: 0.296 AC: 602 AN: 2034

Alfa AF: 0.281 Hom.: 1641

Bravo AF: 0.276

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.77
DANN	Benign	0.44
PhyloP100		-0.091
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11264886; hg19: chr1-153997346;