rs10179791

Variant names:

• chr2-185738891-G-A
• rs10179791
• NM_173651.4:c.-4G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-185738891-G-A
• chr2-185738891-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_173651.4(FSIP2):​c.-4G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,535,366 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0093 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (25 hom.)
• Consequence: FSIP2 NM_173651.4 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.01
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 2-185738891-G-A is Benign according to our data. Variant chr2-185738891-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3039107.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00925 (1409/152280) while in subpopulation AFR AF = 0.0317 (1317/41558). AF 95% confidence interval is 0.0303. There are 27 homozygotes in GnomAd4. There are 668 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173651.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSIP2	NM_173651.4	MANE Select	c.-4G>A		5_prime_UTR	Exon 1 of 23	NP_775922.3	Q5CZC0-1
	FSIP2-AS2	NR_110214.1		n.187+16C>T		intron	N/A
	FSIP2-AS2	NR_110217.1		n.99+1488C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSIP2	ENST00000424728.6	TSL:5 MANE Select	c.-4G>A		5_prime_UTR	Exon 1 of 23	ENSP00000401306.1	Q5CZC0-1
	FSIP2-AS1	ENST00000769859.1		n.95C>T		non_coding_transcript_exon	Exon 1 of 4
	FSIP2-AS1	ENST00000427269.2	TSL:5	n.101+1488C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00919 AC: 1399 AN: 152162 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00185 AC: 238 AN: 128492 AF XY: 0.00135

Gnomad AFR exome AF: 0.0309

Gnomad AMR exome AF: 0.00140

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000188

Gnomad OTH exome AF: 0.000250

GnomAD4 exome AF: 0.00110 AC: 1526 AN: 1383086 Hom.: 25 Cov.: 32 AF XY: 0.000993 AC XY: 678 AN XY: 682468

African (AFR) AF: 0.0359 AC: 1135 AN: 31582

American (AMR) AF: 0.00193 AC: 69 AN: 35678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35726

South Asian (SAS) AF: 0.000189 AC: 15 AN: 79194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33650

Middle Eastern (MID) AF: 0.00145 AC: 8 AN: 5522

European-Non Finnish (NFE) AF: 0.0000853 AC: 92 AN: 1078720

Other (OTH) AF: 0.00358 AC: 207 AN: 57848

GnomAD4 genome AF: 0.00925 AC: 1409 AN: 152280 Hom.: 27 Cov.: 32 AF XY: 0.00897 AC XY: 668 AN XY: 74464

African (AFR) AF: 0.0317 AC: 1317 AN: 41558

American (AMR) AF: 0.00359 AC: 55 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68016

Other (OTH) AF: 0.00992 AC: 21 AN: 2116

Alfa AF: 0.00116 Hom.: 1

Bravo AF: 0.0106

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FSIP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.2
DANN	Benign	0.94
PhyloP100		-1.0
PromoterAI		-0.043	Neutral
Mutation Taster		=100/0	polymorphism

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: rs10179791; hg19: chr2-186603618;