rs237091

chr20-5840539-G-A

Variant summary

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

The NM_152504.4(SHLD1):c.179-22485G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,036 control chromosomes in the GnomAD database, including 3,924 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 0.22 (3924 hom., cov: 32)
• Consequence: SHLD1 NM_152504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHLD1	NM_152504.4	c.179-22485G>A		intron_variant		ENST00000303142.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHLD1	ENST00000303142.11	c.179-22485G>A		intron_variant		1	NM_152504.4	P1
SHLD1	ENST00000442185.1	c.320-22485G>A		intron_variant		3
SHLD1	ENST00000445603.1	c.179-22485G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33527 AN: 151918 Hom.: 3922 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.221 AC: 33544 AN: 152036 Hom.: 3924 Cov.: 32 AF XY: 0.222 AC XY: 16525 AN XY: 74314

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.209

Alfa AF: 0.194 Hom.: 4952

Bravo AF: 0.228

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.1
Dann	Benign	0.77

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: rs237091; hg19: chr20-5821185;