rs1861896

Variant names:

• chr2-185737324-C-T
• rs1861896
• ENST00000421998.6:n.153-1192G>A

Variant summary

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

The ENST00000421998.6(FSIP2-AS1):​n.153-1192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,018 control chromosomes in the GnomAD database, including 8,131 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 0.32 (8131 hom., cov: 32)
• Consequence: FSIP2-AS1 ENST00000421998.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 5 publications found

Genes affected

FSIP2-AS1 (HGNC:40978): (FSIP2 antisense RNA 1)

FSIP2-AS2 (HGNC:54061): (FSIP2 antisense RNA 2)

FSIP2 (HGNC:21675): (fibrous sheath interacting protein 2) This gene encodes a protein associated with the sperm fibrous sheath. Genes encoding most of the fibrous-sheath associated proteins genes are transcribed only during the postmeiotic period of spermatogenesis. The protein encoded by this gene is specific to spermatogenic cells. Copy number variation in this gene may be associated with testicular germ cell tumors. Pseudogenes associated with this gene are reported on chromosomes 2 and X. [provided by RefSeq, Aug 2016]

FSIP2 Gene-Disease associations (from GenCC):

• spermatogenic failure 34

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSIP2-AS2	NR_110214.1	n.188-1187G>A		intron_variant	Intron 1 of 3
FSIP2-AS2	NR_110215.1	n.151-1192G>A		intron_variant	Intron 1 of 3
FSIP2-AS2	NR_110216.1	n.151-1187G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSIP2-AS1	ENST00000421998.6	n.153-1192G>A		intron_variant	Intron 1 of 3	1
FSIP2-AS1	ENST00000427269.2	n.101+3055G>A		intron_variant	Intron 1 of 2	5
FSIP2-AS1	ENST00000437717.1	n.187+862G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48997 AN: 151902 Hom.: 8132 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.322 AC: 48997 AN: 152018 Hom.: 8131 Cov.: 32 AF XY: 0.316 AC XY: 23490 AN XY: 74312

African (AFR) AF: 0.284 AC: 11752 AN: 41426

American (AMR) AF: 0.381 AC: 5823 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1471 AN: 3464

East Asian (EAS) AF: 0.377 AC: 1942 AN: 5156

South Asian (SAS) AF: 0.268 AC: 1295 AN: 4826

European-Finnish (FIN) AF: 0.235 AC: 2486 AN: 10574

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23098 AN: 67990

Other (OTH) AF: 0.352 AC: 744 AN: 2114

Alfa AF: 0.327 Hom.: 1352

Bravo AF: 0.333

Asia WGS AF: 0.296 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.49
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs1861896; hg19: chr2-186602051;