7-96488606-G-C

Variant names:

• chr7-96488606-G-C
• rs4729260
• ENST00000611360.4:n.87-2189C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000611360.4(SEM1):​n.87-2189C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,830 control chromosomes in the GnomAD database, including 39,909 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 0.72 (39909 hom., cov: 30)
• Consequence: SEM1 ENST00000611360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 27 publications found

Genes affected

SEM1 (HGNC:10845): (SEM1 26S proteasome subunit) The product of this gene has been localized within the split hand/split foot malformation locus SHFM1 at chromosome 7. It has been proposed to be a candidate gene for the autosomal dominant form of the heterogeneous limb developmental disorder split hand/split foot malformation type 1. In addition, it has been shown to directly interact with BRCA2. It also may play a role in the completion of the cell cycle. [provided by RefSeq, Jul 2008]

LOC105375411 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000611360.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEM1	NR_163948.1		n.100-2189C>G		intron	N/A
	SEM1	NR_163949.1		n.100-2189C>G		intron	N/A
	SEM1	NR_163950.1		n.537-2189C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEM1	ENST00000611360.4	TSL:1	n.87-2189C>G		intron	N/A
	SEM1	ENST00000356686.2	TSL:5	c.13-2189C>G		intron	N/A	ENSP00000349114.1
	SEM1	ENST00000615352.4	TSL:5	c.13-2189C>G		intron	N/A	ENSP00000481021.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109304 AN: 151712 Hom.: 39846 Cov.: 30

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.721 AC: 109432 AN: 151830 Hom.: 39909 Cov.: 30 AF XY: 0.724 AC XY: 53689 AN XY: 74152

African (AFR) AF: 0.811 AC: 33574 AN: 41406

American (AMR) AF: 0.727 AC: 11075 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2192 AN: 3470

East Asian (EAS) AF: 0.862 AC: 4419 AN: 5128

South Asian (SAS) AF: 0.790 AC: 3801 AN: 4814

European-Finnish (FIN) AF: 0.693 AC: 7273 AN: 10494

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.661 AC: 44895 AN: 67970

Other (OTH) AF: 0.682 AC: 1441 AN: 2112

Alfa AF: 0.660 Hom.: 16316

Bravo AF: 0.725

Asia WGS AF: 0.787 AC: 2737 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		0.24
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: rs4729260; hg19: chr7-96117918;