7-96504219-T-C

Variant names:

• chr7-96504219-T-C
• rs7781370
• ENST00000466986.5:n.*60+2404A>G

Variant summary

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

The ENST00000466986.5(SEM1):​n.*60+2404A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 151,952 control chromosomes in the GnomAD database, including 39,768 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 (39768 hom., cov: 31)
• Consequence: SEM1 ENST00000466986.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• Publications: 33 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000466986.5. 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_163950.1		n.536+2404A>G		intron	N/A
	SEM1	NR_163951.1		n.329+2404A>G		intron	N/A
	SEM1	NR_163952.1		n.458+2404A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEM1	ENST00000466986.5	TSL:2	n.*60+2404A>G		intron	N/A	ENSP00000481400.1
	SEM1	ENST00000613919.4	TSL:2	n.*252+2404A>G		intron	N/A	ENSP00000482085.1
	SEM1	ENST00000617133.4	TSL:2	n.*198+2404A>G		intron	N/A	ENSP00000484726.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109132 AN: 151830 Hom.: 39703 Cov.: 31

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.719 AC: 109264 AN: 151952 Hom.: 39768 Cov.: 31 AF XY: 0.722 AC XY: 53652 AN XY: 74262

African (AFR) AF: 0.809 AC: 33539 AN: 41438

American (AMR) AF: 0.721 AC: 11002 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2189 AN: 3466

East Asian (EAS) AF: 0.869 AC: 4479 AN: 5152

South Asian (SAS) AF: 0.787 AC: 3792 AN: 4818

European-Finnish (FIN) AF: 0.692 AC: 7307 AN: 10566

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44753 AN: 67940

Other (OTH) AF: 0.679 AC: 1433 AN: 2112

Alfa AF: 0.683 Hom.: 102774

Bravo AF: 0.723

Asia WGS AF: 0.790 AC: 2746 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.40
PhyloP100		-0.81

Splicing

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

Other links and lift over

dbSNP: rs7781370; hg19: chr7-96133531;