20-5860978-C-T

Variant names:

• chr20-5860978-C-T
• rs6053753
• NM_152504.4:c.179-2046C>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.179-2046C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 151,190 control chromosomes in the GnomAD database, including 40,304 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 (40304 hom., cov: 29)
• Consequence: SHLD1 NM_152504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 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.179-2046C>T		intron	N/A	NP_689717.2
	SHLD1	NM_001303477.2		c.179-2046C>T		intron	N/A	NP_001290406.1
	SHLD1	NM_001303478.2		c.83-2046C>T		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.179-2046C>T		intron	N/A	ENSP00000305875.6
	SHLD1	ENST00000442185.1	TSL:3	c.320-2046C>T		intron	N/A	ENSP00000410534.1
	SHLD1	ENST00000445603.1	TSL:3	c.179-2046C>T		intron	N/A	ENSP00000399331.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110264 AN: 151078 Hom.: 40276 Cov.: 29

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.730 AC: 110347 AN: 151190 Hom.: 40304 Cov.: 29 AF XY: 0.729 AC XY: 53708 AN XY: 73720

African (AFR) AF: 0.793 AC: 32714 AN: 41236

American (AMR) AF: 0.748 AC: 11346 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2501 AN: 3468

East Asian (EAS) AF: 0.765 AC: 3925 AN: 5130

South Asian (SAS) AF: 0.665 AC: 3170 AN: 4770

European-Finnish (FIN) AF: 0.668 AC: 6832 AN: 10228

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47513 AN: 67888

Other (OTH) AF: 0.727 AC: 1529 AN: 2104

Alfa AF: 0.715 Hom.: 4830

Bravo AF: 0.740

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.66
PhyloP100		0.17
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: rs6053753; hg19: chr20-5841624;