chr7-92447513-C-G

Variant names:

• chr7-92447513-C-G
• rs146395954
• NM_021167.5:c.-217C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_021167.5(GATAD1):​c.-217C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 424,064 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (1 hom.)
• Consequence: GATAD1 NM_021167.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.833
• Publications: 0 publications found

Genes affected

GATAD1 (HGNC:29941): (GATA zinc finger domain containing 1) The protein encoded by this gene contains a zinc finger at the N-terminus, and is thought to bind to a histone modification site that regulates gene expression. Mutations in this gene have been associated with autosomal recessive dilated cardiomyopathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

GATAD1 Gene-Disease associations (from GenCC):

• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy 2B

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

TMBIM7P (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 7-92447513-C-G is Benign according to our data. Variant chr7-92447513-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1316287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021167.5. 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
	GATAD1	NM_021167.5	MANE Select	c.-217C>G		5_prime_UTR	Exon 1 of 5	NP_066990.3
	GATAD1	NR_052016.2		n.32C>G		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD1	ENST00000287957.5	TSL:1 MANE Select	c.-217C>G		5_prime_UTR	Exon 1 of 5	ENSP00000287957.3	Q8WUU5
	GATAD1	ENST00000645746.1		n.-217C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000493785.1	A0A2R8Y4H1
	GATAD1	ENST00000645746.1		n.-217C>G		5_prime_UTR	Exon 1 of 6	ENSP00000493785.1	A0A2R8Y4H1

Frequencies

GnomAD3 genomes AF: 0.00259 AC: 394 AN: 152218 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00209

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00231 AC: 627 AN: 271728 Hom.: 1 Cov.: 5 AF XY: 0.00225 AC XY: 315 AN XY: 140302

African (AFR) AF: 0.000163 AC: 1 AN: 6132

American (AMR) AF: 0.000211 AC: 1 AN: 4744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7340

East Asian (EAS) AF: 0.00 AC: 0 AN: 15450

South Asian (SAS) AF: 0.0000600 AC: 1 AN: 16662

European-Finnish (FIN) AF: 0.0147 AC: 248 AN: 16876

Middle Eastern (MID) AF: 0.000864 AC: 1 AN: 1158

European-Non Finnish (NFE) AF: 0.00184 AC: 347 AN: 188974

Other (OTH) AF: 0.00195 AC: 28 AN: 14392

GnomAD4 genome AF: 0.00259 AC: 394 AN: 152336 Hom.: 4 Cov.: 33 AF XY: 0.00346 AC XY: 258 AN XY: 74494

African (AFR) AF: 0.0000962 AC: 4 AN: 41586

American (AMR) AF: 0.000196 AC: 3 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.0229 AC: 243 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00209 AC: 142 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000757 Hom.: 0

Bravo AF: 0.000914

ClinVar

ClinVar submissions as Germline

Significance: Likely 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	-0.78
CADD	Benign	4.4
DANN	Benign	0.65
PhyloP100		-0.83
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs146395954; hg19: chr7-92076827;