20-5861448-G-T

Variant names:

• chr20-5861448-G-T
• rs1632590
• NM_152504.4:c.179-1576G>T

Variant summary

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

The NM_152504.4(SHLD1):​c.179-1576G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,184 control chromosomes in the GnomAD database, including 40,374 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 0.73 (40374 hom., cov: 34)
• Consequence: SHLD1 NM_152504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHLD1	NM_152504.4	c.179-1576G>T		intron_variant	Intron 2 of 2	ENST00000303142.11	NP_689717.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHLD1	ENST00000303142.11	c.179-1576G>T		intron_variant	Intron 2 of 2	1	NM_152504.4	ENSP00000305875.6
SHLD1	ENST00000442185.1	c.320-1576G>T		intron_variant	Intron 3 of 3	3		ENSP00000410534.1
SHLD1	ENST00000445603.1	c.179-1576G>T		intron_variant	Intron 3 of 3	3		ENSP00000399331.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110539 AN: 152066 Hom.: 40344 Cov.: 34

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.727 AC: 110624 AN: 152184 Hom.: 40374 Cov.: 34 AF XY: 0.724 AC XY: 53894 AN XY: 74398

African (AFR) AF: 0.792 AC: 32882 AN: 41514

American (AMR) AF: 0.745 AC: 11390 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2499 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3915 AN: 5176

South Asian (SAS) AF: 0.659 AC: 3183 AN: 4830

European-Finnish (FIN) AF: 0.654 AC: 6923 AN: 10582

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47482 AN: 67994

Other (OTH) AF: 0.724 AC: 1532 AN: 2116

Alfa AF: 0.708 Hom.: 125402

Bravo AF: 0.739

Asia WGS AF: 0.722 AC: 2508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.84
DANN	Benign	0.77
PhyloP100		0.11
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: rs1632590; hg19: chr20-5842094;