rs4785204

Variant names:

• chr16-50069823-C-T
• rs4785204
• NM_182922.4:c.400-355C>T

Variant summary

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

The NM_182922.4(HEATR3):​c.400-355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,174 control chromosomes in the GnomAD database, including 687 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 0.088 (687 hom., cov: 32)
• Consequence: HEATR3 NM_182922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 29 publications found

Genes affected

HEATR3 (HGNC:26087): (HEAT repeat containing 3) The protein encoded by this gene plays a role in ribosomal protein transport and in the assembly of the 5S ribonucleoprotein particle (5S RNP). The encoded protein also may be involved in NOD2-mediated NF-kappaB signaling. [provided by RefSeq, Jul 2016]

HEATR3 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 21

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182922.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR3	NM_182922.4	MANE Select	c.400-355C>T		intron	N/A	NP_891552.1	Q7Z4Q2-1
	HEATR3	NM_001329729.2		c.49-355C>T		intron	N/A	NP_001316658.1
	HEATR3	NM_001329730.2		c.49-355C>T		intron	N/A	NP_001316659.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR3	ENST00000299192.8	TSL:1 MANE Select	c.400-355C>T		intron	N/A	ENSP00000299192.7	Q7Z4Q2-1
	HEATR3	ENST00000887924.1		c.400-355C>T		intron	N/A	ENSP00000557983.1
	HEATR3	ENST00000887923.1		c.400-355C>T		intron	N/A	ENSP00000557982.1

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13416 AN: 152056 Hom.: 690 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0835

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

GnomAD4 genome AF: 0.0882 AC: 13423 AN: 152174 Hom.: 687 Cov.: 32 AF XY: 0.0879 AC XY: 6538 AN XY: 74404

African (AFR) AF: 0.0940 AC: 3902 AN: 41510

American (AMR) AF: 0.0979 AC: 1497 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 155 AN: 3472

East Asian (EAS) AF: 0.258 AC: 1335 AN: 5170

South Asian (SAS) AF: 0.0975 AC: 470 AN: 4820

European-Finnish (FIN) AF: 0.0458 AC: 486 AN: 10606

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0786 AC: 5343 AN: 68000

Other (OTH) AF: 0.0850 AC: 179 AN: 2106

Alfa AF: 0.0863 Hom.: 1257

Bravo AF: 0.0959

Asia WGS AF: 0.157 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		0.010
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: rs4785204; hg19: chr16-50103734;