7-96491363-G-C

Variant names:

• chr7-96491363-G-C
• rs4727338
• ENST00000611360.4:n.86+4921C>G

Variant summary

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

The ENST00000611360.4(SEM1):​n.86+4921C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,182 control chromosomes in the GnomAD database, including 39,902 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 (39902 hom., cov: 33)
• Consequence: SEM1 ENST00000611360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 28 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEM1	NR_163948.1	n.99+4921C>G		intron_variant	Intron 2 of 4
SEM1	NR_163949.1	n.99+4921C>G		intron_variant	Intron 2 of 3
SEM1	NR_163950.1	n.537-4946C>G		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEM1	ENST00000611360.4	n.86+4921C>G		intron_variant	Intron 2 of 3	1
SEM1	ENST00000356686.2	c.12+4921C>G		intron_variant	Intron 1 of 3	5		ENSP00000349114.1
SEM1	ENST00000615352.4	c.12+4921C>G		intron_variant	Intron 1 of 2	5		ENSP00000481021.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109401 AN: 152064 Hom.: 39839 Cov.: 33

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.720 AC: 109529 AN: 152182 Hom.: 39902 Cov.: 33 AF XY: 0.723 AC XY: 53794 AN XY: 74396

African (AFR) AF: 0.811 AC: 33667 AN: 41536

American (AMR) AF: 0.722 AC: 11036 AN: 15282

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

East Asian (EAS) AF: 0.868 AC: 4502 AN: 5186

South Asian (SAS) AF: 0.788 AC: 3798 AN: 4820

European-Finnish (FIN) AF: 0.692 AC: 7332 AN: 10590

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

European-Non Finnish (NFE) AF: 0.659 AC: 44797 AN: 67988

Other (OTH) AF: 0.680 AC: 1433 AN: 2106

Alfa AF: 0.695 Hom.: 3808

Bravo AF: 0.724

Asia WGS AF: 0.790 AC: 2746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.7
DANN	Benign	0.22
PhyloP100		0.42
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: rs4727338; hg19: chr7-96120675;