20-5859893-A-G

Position:

• chr20-5859893-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152504.4(SHLD1):​c.179-3131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,240 control chromosomes in the GnomAD database, including 1,600 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 0.13 (1600 hom., cov: 32)
• Consequence: SHLD1 NM_152504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62

Genes affected

SHLD1 (HGNC:26318): (shieldin complex subunit 1) Involved in negative regulation of double-strand break repair via homologous recombination; positive regulation of double-strand break repair via nonhomologous end joining; and positive regulation of isotype switching. Located in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHLD1	NM_152504.4	c.179-3131A>G		intron_variant		ENST00000303142.11	NP_689717.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHLD1	ENST00000303142.11	c.179-3131A>G		intron_variant		1	NM_152504.4	ENSP00000305875.6
SHLD1	ENST00000442185.1	c.320-3131A>G		intron_variant		3		ENSP00000410534.1
SHLD1	ENST00000445603.1	c.179-3131A>G		intron_variant		3		ENSP00000399331.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20165 AN: 152122 Hom.: 1599 Cov.: 32

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0604

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.132 AC: 20161 AN: 152240 Hom.: 1600 Cov.: 32 AF XY: 0.133 AC XY: 9898 AN XY: 74422

Gnomad4 AFR AF: 0.0491

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0610

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.118

Alfa AF: 0.161 Hom.: 3804

Bravo AF: 0.128

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs4815868; hg19: chr20-5840539;