1-114875888-C-G

Variant names:

• chr1-114875888-C-G
• rs2274118
• NM_003176.4:c.658-181C>G

Variant summary

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

The NM_003176.4(SYCP1):​c.658-181C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,112 control chromosomes in the GnomAD database, including 4,110 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 0.21 (4110 hom., cov: 33)
• Consequence: SYCP1 NM_003176.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 5 publications found

Genes affected

SYCP1 (HGNC:11487): (synaptonemal complex protein 1) Enables double-stranded DNA binding activity. Involved in protein homotetramerization. Predicted to be located in synaptonemal complex. Predicted to be active in central element; male germ cell nucleus; and transverse filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003176.4. 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
	SYCP1	NM_003176.4	MANE Select	c.658-181C>G		intron	N/A	NP_003167.2
	SYCP1	NM_001282541.2		c.658-181C>G		intron	N/A	NP_001269470.1	A0A024R0I2
	SYCP1	NM_001282542.2		c.658-181C>G		intron	N/A	NP_001269471.1	A0A087WZC3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCP1	ENST00000369522.8	TSL:1 MANE Select	c.658-181C>G		intron	N/A	ENSP00000358535.3	Q15431
	SYCP1	ENST00000618516.4	TSL:1	c.658-181C>G		intron	N/A	ENSP00000480997.1	Q15431
	SYCP1	ENST00000613524.4	TSL:1	c.658-181C>G		intron	N/A	ENSP00000482532.1	A0A087WZC3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31157 AN: 151994 Hom.: 4102 Cov.: 33

Gnomad AFR AF: 0.0500

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.205 AC: 31185 AN: 152112 Hom.: 4110 Cov.: 33 AF XY: 0.213 AC XY: 15820 AN XY: 74346

African (AFR) AF: 0.0499 AC: 2072 AN: 41526

American (AMR) AF: 0.298 AC: 4544 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3466

East Asian (EAS) AF: 0.349 AC: 1803 AN: 5170

South Asian (SAS) AF: 0.348 AC: 1677 AN: 4822

European-Finnish (FIN) AF: 0.308 AC: 3254 AN: 10552

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16346 AN: 67982

Other (OTH) AF: 0.217 AC: 459 AN: 2116

Alfa AF: 0.113 Hom.: 211

Bravo AF: 0.198

Asia WGS AF: 0.360 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.53
PhyloP100		-0.44
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: rs2274118; hg19: chr1-115418509;