19-49930940-C-T

Variant names:

• chr19-49930940-C-T
• rs12449
• NM_001193646.2:c.90C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001193646.2(ATF5):​c.90C>T​(p.Leu30Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0034 in 1,602,986 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (95 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (92 hom.)
• Consequence: ATF5 NM_001193646.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.93
• Publications: 3 publications found

Genes affected

ATF5 (HGNC:790): (activating transcription factor 5) Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II transcription regulatory region sequence-specific DNA binding activity; and tubulin binding activity. Involved in several processes, including fat cell differentiation; regulation of cell cycle process; and regulation of transcription, DNA-templated. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269179 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 19-49930940-C-T is Benign according to our data. Variant chr19-49930940-C-T is described in ClinVar as Benign. ClinVar VariationId is 782656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193646.2. 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
	ATF5	NM_001193646.2	MANE Select	c.90C>T	p.Leu30Leu	synonymous	Exon 2 of 3	NP_001180575.1	Q9Y2D1
	ATF5	NM_001290746.2		c.90C>T	p.Leu30Leu	synonymous	Exon 2 of 3	NP_001277675.1	Q9Y2D1
	ATF5	NM_012068.6		c.90C>T	p.Leu30Leu	synonymous	Exon 3 of 4	NP_036200.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF5	ENST00000423777.7	TSL:1 MANE Select	c.90C>T	p.Leu30Leu	synonymous	Exon 2 of 3	ENSP00000396954.1	Q9Y2D1
	ENSG00000269179	ENST00000451973.1	TSL:2	n.*77+20951G>A		intron	N/A	ENSP00000391489.1	H7BZU6
	ATF5	ENST00000595125.5	TSL:2	c.90C>T	p.Leu30Leu	synonymous	Exon 3 of 4	ENSP00000470633.1	Q9Y2D1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2735 AN: 152166 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00475 AC: 1090 AN: 229380 AF XY: 0.00345

Gnomad AFR exome AF: 0.0699

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000584

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000972

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00186 AC: 2695 AN: 1450702 Hom.: 92 Cov.: 31 AF XY: 0.00158 AC XY: 1140 AN XY: 720904

African (AFR) AF: 0.0678 AC: 2255 AN: 33278

American (AMR) AF: 0.00288 AC: 124 AN: 42990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25710

East Asian (EAS) AF: 0.00 AC: 0 AN: 39176

South Asian (SAS) AF: 0.000178 AC: 15 AN: 84186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52688

Middle Eastern (MID) AF: 0.00354 AC: 20 AN: 5646

European-Non Finnish (NFE) AF: 0.0000443 AC: 49 AN: 1107084

Other (OTH) AF: 0.00387 AC: 232 AN: 59944

GnomAD4 genome AF: 0.0181 AC: 2750 AN: 152284 Hom.: 95 Cov.: 32 AF XY: 0.0173 AC XY: 1285 AN XY: 74462

African (AFR) AF: 0.0636 AC: 2644 AN: 41552

American (AMR) AF: 0.00431 AC: 66 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68010

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.00873 Hom.: 14

Bravo AF: 0.0202

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=99/1	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: rs12449; hg19: chr19-50434197;