1-41223266-C-T

Variant names:

• chr1-41223266-C-T
• rs11209718
• NM_001394311.1:c.-118+18793G>A

Variant summary

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

The NM_001394311.1(SCMH1):​c.-118+18793G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,054 control chromosomes in the GnomAD database, including 11,014 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 0.36 (11014 hom., cov: 32)
• Consequence: SCMH1 NM_001394311.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 16 publications found

Genes affected

SCMH1 (HGNC:19003): (Scm polycomb group protein homolog 1) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to act upstream of or within anterior/posterior pattern specification; chromatin remodeling; and spermatogenesis. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [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=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394311.1. 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
	SCMH1	NM_001394311.1	MANE Select	c.-118+18793G>A		intron	N/A	NP_001381240.1	A0A8Q3SHN2
	SCMH1	NM_001031694.3		c.-500+18793G>A		intron	N/A	NP_001026864.1	Q96GD3-1
	SCMH1	NM_001394300.1		c.-701+18793G>A		intron	N/A	NP_001381229.1	Q96GD3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCMH1	ENST00000695335.1	MANE Select	c.-118+18793G>A		intron	N/A	ENSP00000511813.1	A0A8Q3SHN2
	SCMH1	ENST00000372597.5	TSL:1	c.-427+18793G>A		intron	N/A	ENSP00000361678.1	Q96GD3-4
	SCMH1	ENST00000372596.5	TSL:1	c.-540+18793G>A		intron	N/A	ENSP00000361677.1	Q96GD3-5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54150 AN: 151934 Hom.: 11011 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.356 AC: 54158 AN: 152054 Hom.: 11014 Cov.: 32 AF XY: 0.362 AC XY: 26876 AN XY: 74320

African (AFR) AF: 0.157 AC: 6525 AN: 41480

American (AMR) AF: 0.505 AC: 7721 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2141 AN: 5176

South Asian (SAS) AF: 0.334 AC: 1610 AN: 4816

European-Finnish (FIN) AF: 0.439 AC: 4628 AN: 10544

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28941 AN: 67966

Other (OTH) AF: 0.376 AC: 794 AN: 2114

Alfa AF: 0.387 Hom.: 19854

Bravo AF: 0.357

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.58
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11209718; hg19: chr1-41688938;