4-158966705-A-G

Position:

• chr4-158966705-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152543.3(C4orf45):​c.298-6361T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 152,376 control chromosomes in the GnomAD database, including 75,969 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 1.0 (75969 hom., cov: 33)
• Consequence: C4orf45 NM_152543.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492

Genes affected

C4orf45 (HGNC:):

SPMIP2 (HGNC:26342): (sperm microtubule inner protein 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C4orf45	NM_152543.3	c.298-6361T>C		intron_variant		ENST00000434826.3	NP_689756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPMIP2	ENST00000434826.3	c.298-6361T>C		intron_variant		2	NM_152543.3	ENSP00000412215	P1
SPMIP2	ENST00000505647.1	n.53+6374T>C		intron_variant, non_coding_transcript_variant		3
SPMIP2	ENST00000508011.1	n.392+6374T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.999 AC: 152037 AN: 152258 Hom.: 75910 Cov.: 33

Gnomad AFR AF: 0.997

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.997

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

GnomAD4 genome AF: 0.999 AC: 152155 AN: 152376 Hom.: 75969 Cov.: 33 AF XY: 0.999 AC XY: 74415 AN XY: 74514

Gnomad4 AFR AF: 0.997

Gnomad4 AMR AF: 0.999

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.997

Alfa AF: 0.999 Hom.: 3321

Bravo AF: 0.998

Asia WGS AF: 0.999 AC: 3473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs471982; hg19: chr4-159887857;