NM_001354761.2:c.837T>C

Variant names:

• chr4-2898279-T-C
• rs144809220
• NM_001354761.2:c.837T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001354761.2(ADD1):​c.837T>C​(p.Asp279Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00074 in 1,614,172 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (4 hom.)
• Consequence: ADD1 NM_001354761.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.502
• Publications: 3 publications found

Genes affected

ADD1 (HGNC:243): (adducin 1) Adducins are a family of cytoskeletal proteins encoded by three genes (alpha, beta, and gamma). Adducin acts as a heterodimer of the related alpha, beta, or gamma subunits. The protein encoded by this gene represents the alpha subunit. Alpha- and beta-adducin include a protease-resistant N-terminal region and a protease-sensitive, hydrophilic C-terminal region. Adducin binds with high affinity to Ca(2+)/calmodulin and is a substrate for protein kinases A and C. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 4-2898279-T-C is Benign according to our data. Variant chr4-2898279-T-C is described in ClinVar as Benign. ClinVar VariationId is 790309.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.502 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354761.2. 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
	ADD1	NM_001354761.2	MANE Select	c.837T>C	p.Asp279Asp	synonymous	Exon 7 of 16	NP_001341690.1	A0A804HL01
	ADD1	NM_001354756.2		c.837T>C	p.Asp279Asp	synonymous	Exon 7 of 16	NP_001341685.1
	ADD1	NM_014189.4		c.837T>C	p.Asp279Asp	synonymous	Exon 7 of 15	NP_054908.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADD1	ENST00000683351.1	MANE Select	c.837T>C	p.Asp279Asp	synonymous	Exon 7 of 16	ENSP00000508142.1	A0A804HL01
	ADD1	ENST00000355842.7	TSL:1	c.837T>C	p.Asp279Asp	synonymous	Exon 8 of 18	ENSP00000348100.3	P35611-4
	ADD1	ENST00000398123.6	TSL:1	c.837T>C	p.Asp279Asp	synonymous	Exon 6 of 15	ENSP00000381191.2	P35611-6

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 164 AN: 152160 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000966 AC: 243 AN: 251468 AF XY: 0.000905

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000677

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000703 AC: 1028 AN: 1461894 Hom.: 4 Cov.: 31 AF XY: 0.000723 AC XY: 526 AN XY: 727248

African (AFR) AF: 0.000806 AC: 27 AN: 33480

American (AMR) AF: 0.00315 AC: 141 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.000893 AC: 77 AN: 86258

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53420

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5768

European-Non Finnish (NFE) AF: 0.000546 AC: 607 AN: 1112012

Other (OTH) AF: 0.00215 AC: 130 AN: 60396

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152278 Hom.: 1 Cov.: 32 AF XY: 0.00110 AC XY: 82 AN XY: 74454

African (AFR) AF: 0.00101 AC: 42 AN: 41554

American (AMR) AF: 0.00353 AC: 54 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4828

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68032

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.000766 Hom.: 0

Bravo AF: 0.00126

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000711

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.1
DANN	Benign	0.53
PhyloP100		0.50
PromoterAI		0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs144809220; hg19: chr4-2900006;