20-5861872-T-C

Variant names:

• chr20-5861872-T-C
• rs6053754
• NM_152504.4:c.179-1152T>C

Variant summary

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

The NM_152504.4(SHLD1):​c.179-1152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,040 control chromosomes in the GnomAD database, including 7,250 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 0.30 (7250 hom., cov: 32)
• Consequence: SHLD1 NM_152504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.441 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.179-1152T>C		intron	N/A	NP_689717.2
	SHLD1	NM_001303477.2		c.179-1152T>C		intron	N/A	NP_001290406.1
	SHLD1	NM_001303478.2		c.83-1152T>C		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.179-1152T>C		intron	N/A	ENSP00000305875.6
	SHLD1	ENST00000442185.1	TSL:3	c.320-1152T>C		intron	N/A	ENSP00000410534.1
	SHLD1	ENST00000445603.1	TSL:3	c.179-1152T>C		intron	N/A	ENSP00000399331.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46144 AN: 151922 Hom.: 7233 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.304 AC: 46194 AN: 152040 Hom.: 7250 Cov.: 32 AF XY: 0.304 AC XY: 22589 AN XY: 74334

African (AFR) AF: 0.302 AC: 12534 AN: 41458

American (AMR) AF: 0.377 AC: 5762 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 879 AN: 3470

East Asian (EAS) AF: 0.456 AC: 2357 AN: 5170

South Asian (SAS) AF: 0.361 AC: 1737 AN: 4818

European-Finnish (FIN) AF: 0.219 AC: 2318 AN: 10576

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19653 AN: 67952

Other (OTH) AF: 0.325 AC: 686 AN: 2110

Alfa AF: 0.294 Hom.: 19477

Bravo AF: 0.316

Asia WGS AF: 0.433 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.33
PhyloP100		0.26
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: rs6053754; hg19: chr20-5842518;