rs237091

Variant names:

• chr20-5840539-G-A
• rs237091
• NM_152504.4:c.179-22485G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

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 = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152504.4. 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
	SHLD1	NM_152504.4	MANE Select	c.179-22485G>A		intron	N/A	NP_689717.2
	SHLD1	NM_001303477.2		c.179-22485G>A		intron	N/A	NP_001290406.1
	SHLD1	NM_001303478.2		c.83-22485G>A		intron	N/A	NP_001290407.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHLD1	ENST00000303142.11	TSL:1 MANE Select	c.179-22485G>A		intron	N/A	ENSP00000305875.6
	SHLD1	ENST00000442185.1	TSL:3	c.320-22485G>A		intron	N/A	ENSP00000410534.1
	SHLD1	ENST00000445603.1	TSL:3	c.179-22485G>A		intron	N/A	ENSP00000399331.1

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

African (AFR) AF: 0.271 AC: 11240 AN: 41460

American (AMR) AF: 0.269 AC: 4107 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3468

East Asian (EAS) AF: 0.279 AC: 1443 AN: 5172

South Asian (SAS) AF: 0.218 AC: 1052 AN: 4820

European-Finnish (FIN) AF: 0.191 AC: 2010 AN: 10544

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12515 AN: 67980

Other (OTH) AF: 0.209 AC: 441 AN: 2112

Alfa AF: 0.200 Hom.: 8835

Bravo AF: 0.228

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.77
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs237091; hg19: chr20-5821185;